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Intracerebral hemorrhage (ICH) is a common neurological condition that causes severe disability and even death. Even though the mechanism is not clear, increasing evidence shows the efficacy of atorvastatin on treating ICH. In this study, we examined the impact of atorvastatin on the NOD-like receptor protein 3 (NLRP3) inflammasome and inflammatory pathways following ICH. Mouse models of ICH were established by collagenase injection in adult C57BL/6 mice. IHC mice received atorvastatin treatment 2 h after hematoma establishment. First, the changes of glial cells and neurons in the brains of ICH patients and mice were detected by immunohistochemistry and western blotting. Second, the molecular mechanisms underlying the microglial activation and neuronal loss were evaluated after the application of atorvastatin. Finally, the behavioral deficits of ICH mice without or with the treatment of atorvastatin were determined by neurological defect scores. The results demonstrated that atorvastatin significantly deactivated glial cells by reducing the expression of glial fibrillary acidic protein (GFAP), Ionized calcium binding adapter molecule 1 (Iba1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in ICH model mice. For inflammasomes, atorvastatin also showed its efficacy by decreasing the expression of NLRP3, cleaved caspase-1, and IL-1β in ICH mice. Moreover, atorvastatin markedly inhibited the upregulation of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88), which indicated deactivation of NLRP3 inflammasomes. By inhibiting the activities of inflammasomes in glial cells, neuronal loss was partially prevented by suppressing the apoptosis in the brains of ICH mice, protecting them from neurological defects.

To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD).A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed.A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P0.01).The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.

To assess the value of low-depth whole-genome copy number variation sequencing (CNV-seq) for the analysis of chromosomal copy number variations among fetuses with echogenic bowel (EB).A total of 163 fetuses were included in this study. Amniotic fluid (162 cases) or chorionic villi (1 case) were collected and subjected to CNV-seq for the analysis of CNVs.Thirteen (8.0%) pathogenic CNVs were detected, including 9 (5.5%) aneuploidies and 4 (2.4%) CNVs. The detection rate of the isolated EB group and combined EB group were 1.7% (1/58) and 11.4% (12/105), respectively. There was a significant difference between the two groups (P0.05). A Xp22.1 duplication was detected in both groups, and the fetuses were predicted as female DMD carriers and born healthy. Nine cases of aneuploidies and 2 (likely) pathogenic CNVs were identified in the combined EB group, all of them have warranted induced labor.The prevalence of chromosomal aneuploidies and pathogenic CNVs in fetuses with combined EB was much higher than isolated EB, and most of them may warrant termination of pregnancy. Compared with isolated EB, more attention should be paid to combined EB, for which prenatal diagnosis and genetic counseling should be carried out in time.

Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo.This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients.48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd).Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p 0.05). No difference was seen between Group A and Group B or Group A and Group C (p 0.05). More patients complained higher pain score in Group A as compared with Group C (p 0.05).The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%.

Urinalysis is attractive in non-invasive early diagnosis of bladder cancer compared with clinical gold standard cystoscopy. However, the trace bladder tumor biomarkers in urine and the particularly complex urine environment pose significant challenges for urinalysis. Here, a clinically adoptable urinalysis device that integrates molecular-specificity indium gallium zinc oxide field-effect transistor (IGZO FET) biosensor arrays, a device control panel, and an internet terminal for directly analyzing five bladder-tumor-associated proteins in clinical urine samples, is reported for bladder cancer diagnosis and classification. The IGZO FET biosensors with engineered sensing interfaces provide high sensitivity and selectivity for identification of trace proteins in the complex urine environment. Integrating with a machine-learning algorithm, this device can identify bladder cancer with an accuracy of 95.0% in a cohort of 197 patients and 75 non-bladder cancer individuals, distinguishing cancer stages with an overall accuracy of 90.0% and assessing bladder cancer recurrence after surgical treatment. The non-invasive urinalysis device defines a robust technology for remote healthcare and personalized medicine.

Background Persistent infection by high-risk human papillomavirus (HPV) is the leading cause of cervical intraepithelial neoplasia and cervical carcinoma. Local hyperthermia at 44ºC has been proven efficacious to clear cutaneous or anogenital warts caused by HPV infection. This study aims to assess the effect of hyperthermia at 44ºC on the clearance of high-risk HPV. Methods A randomized, patient-blind, sham treatment–controlled trial was conducted in 4 medical centers. We enrolled patients with positive high-risk HPVs and normal or insignificant cytological findings (negative/atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). Participants were randomly assigned (1:1) to receive either hyperthermia at 44ºC or 37ºC, for 30 minutes in each session. Patients in both groups received treatment once a day for 3 consecutive days, plus 2 more sessions 10 ± 3 days later. The primary outcome was clearance rate of HPV 3 months after treatment. Results After a 3-month follow-up, hyperthermia treatment at 44ºC and 37ºC achieved HPV clearance rates of 85.19% (23/27) and 50% (13/26), respectively (P = .014). There was no significant difference of treatment response between patients with single and multiple type of HPV by 44ºC hyperthermia treatment. There were no significant adverse events recorded during the treatment period in both groups. Conclusions Local hyperthermia at 44ºC safely and significantly aids in clearing cervical high-risk HPVs, the effect of which helps halt the progression of cervical transformation and transmission of the virus. Clinical Trials Registration NCT03436251.

Background and aims Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: β = − 0.50, P β = − 0.14, P = 0.087; CT: β = − 0.20, P = 0.011; TT: β = − 1.19, P P for difference P for difference P for difference = 0.757). Conclusions Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Background. Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia. Methods. Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein. Results. DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P

Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point–dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up‐regulation of miR‐27a‐5p and the latter could down‐regulate SMAD2, and these results were verified by qRT‐PCR or Western blot. Furthermore, UVA radiation (5 J/cm2), knocking down SIRT1 or overexpression of miR‐27a‐5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR‐27a‐5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR‐27a‐5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1‐miR‐27a‐5p‐SMAD2‐MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA‐induced skin damage.

Background Human papillomaviruses (HPVs), a group of non-enveloped small viruses with double-stranded circular DNA which lead to multiple skin diseases such as benign warts, are commonly seen in clinics. The current HPV detection systems aim mainly at mucosal HPVs, however, an efficient clinical approach for cutaneous HPVs detection is lacking. Objectives To establish a rapid detection system for cutaneous HPVs using a colorimetric loop-mediated isothermal amplification (LAMP) with hydroxynaphthol blue (HNB) dye in combination with microfluidic technology. Methods L1 DNA sequences of the 30 cutaneous HPVs were chemically synthesized, and LAMP primers against L1 DNA were designed with use of an online LAMP designing tool. Isothermal amplification was performed with use of a water bath and the amplification results were inspected with the naked eye. Using PCR sequencing as a control method, the specificity and sensitivity of the new detection system were obtained by detecting clinical samples. Results The lower detection limit of the LAMP assay was 107 viral DNA copies/μl when tested on synthesized L1 DNA sequences, which was better than the conventional PCR. Compared to PCR sequencing, the sensitivity of HPV27, HPV2, HPV1, HPV57, HPV3, HPV4, HPV7 and HPV75 genotypes detections were 100%, whereas the specificity was 34.55, 45.12, 95.83, 98.59 and 97.62% respectively, when tested on clinical samples. Conclusions The new cutaneous type HPV detection system is characterized by both a good sensitivity and specificity compared to conventional methods.

The World Health Organization (WHO) has deemed coronavirus disease 2019 (COVID-19) to be a pandemic. The strict prevention and control measures taken by China have proven to be effective, creating a window of opportunity for other countries. The tracking and management of contacts of patients with COVID-19 are important components of prevention and control measures. This article briefly describes the placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in China from the perspective of frontline staff. This article focuses on a community in the Jiading District of Shanghai to provide a reference for placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in other countries and regions.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

Background Hyperthermia upregulates DNAJA4, a member of heat shock proteins (HSPs) 40 family, in human keratinocytes and HPV-infected tissue. DNAJA4 deficiency enhances growth arrest induced by hyperthermia. Clusterin (CLU) and phosphorylated ERK (p-ERK) play a role in regulating cell proliferation and apoptosis, under environmental stress. Objectives To examine the downstream molecules and signalling pathways of DNAJA4 and assess their roles in cell cycle and apoptosis of keratinocytes in response to hyperthermia. Methods Wild-type and DNAJA4-knockout (KO) HaCaT cells were exposed to either 44 °C (hyperthermia) or 37 °C (control) for 30 min. The expression levels of CLU and p-ERK were determined by RT-PCR and Western blotting. RNAi and PD98059 were used to inhibit the expression of CLU and p-ERK, respectively. Cell viability, cell cycle and apoptosis were analysed by MTS assay and flow cytometry. Fresh biopsy samples of human normal foreskin or condyloma acuminatum (CA) were utilized to examine the expression of CLU and p-ERK after ex vivo culture at 44 °C. Results The expression of CLU and p-ERK was significantly increased by hyperthermia treatment at 44 °C in HaCaT cells, foreskin and HPV-infected tissues. In HaCaT cells subjected to hyperthermia, DNAJA4 deficiency further augmented the expression of CLU and p-ERK. CLU deficiency enhanced the p-ERK expression. Hyperthermia-induced CLU and p-ERK exerted protective roles mainly through inhibiting apoptosis and maintaining cell cycle, respectively. Conclusions In keratinocytes, CLU and p-ERK are induced by hyperthermia, an effect which can be further enhanced by DNAJA4 deficiency. CLU deficiency also increases p-ERK expression. Both CLU and p-ERK are critical protective factors of human keratinocytes from hyperthermia-induced injury.

Background: In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth.Objective: A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Methods: Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group 3 during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopec...

Currently, vision-related neuroscience studies are undergoing a trend from simplified image stimuli toward more naturalistic stimuli. Virtual reality (VR), as an emerging technology for visual immersion, provides more depth cues for three-dimensional (3D) presentation than two-dimensional (2D) image. It is still unclear whether the depth cues used to create 3D visual perception modulate specific cortical activation. Here, we constructed two visual stimuli presented by stereoscopic vision in VR and graphical projection with 2D image, respectively, and used electroencephalography to examine neural oscillations and their functional connectivity during 3D perception. We find that neural oscillations are specific to delta and theta bands in stereoscopic vision and the functional connectivity in the two bands increase in cortical areas related to visual pathways. These findings indicate that low-frequency oscillations play an important role in 3D perception with depth cues.

Pain is an integrative phenomenon coupled with dynamic interactions between sensory and contextual processes in the brain, often associated with detectable neurophysiological changes. Recent advances in brain activity recording tools and machine learning technologies have intrigued research and development of neurocomputing techniques for objective and neurophysiology-based pain detection. This paper proposes a pain detection framework based on Electroencephalogram (EEG) and deep convolutional neural networks (CNN). The feasibility of CNN is investigated for distinguishing induced pain state from resting state in the recruitment of 10 chronic back pain patients. The experimental study recorded EEG signals in two phases: 1. movement stimulation (MS), where induces back pain by executing predefined movement tasks; 2. video stimulation (VS), where induces back pain perception by watching a set of video clips. A multi-layer CNN classifies the EEG segments during the resting state and the pain state. The novel approach offers high and robust performance and hence is significant in building a powerful pain detection algorithm. The area under the receiver operating characteristic curve (AUC) of our approach is 0.83 ± 0.09 and 0.81 ± 0.15, in MS and VS, respectively, higher than the state-of-the-art approaches. The sub-brain-areas are also analyzed, to examine distinct brain topographies relevant for pain detection. The results indicate that MS-induced pain tends to evoke a generalized brain area, while the evoked area is relatively partial under VS-induced pain. This work may provide a new solution for researchers and clinical practitioners on pain detection. Published version

To analyze the clinical symptom and parental origin of patients with MECP2 duplication syndrome in order to provide a basis for genetic counseling and prenatal diagnosis.Clinical symptoms of four patients who were diagnosed with MECP2 duplication syndrome by copy number variation sequencing (CNV-Seq) were reviewed. The maternal origin of the duplications were verified.All patients were males, and CNV-Seq revealed that they have all harbored a duplication in the Xq28 region spanning 0.32 ~ 0.86 Mb, which were derived from asymptomatic mothers. The clinical symptoms of three patients with three copies included delayed speech, intellectual disability, and muscular hypotonia, while the patient with four copies had died at 6 months after birth, with clinical symptoms including recurrent infections, seizures, and spasticity.The four cases of MECP2 duplication syndrome have shown complete penetrance and have all derived from asymptomatic mothers. As a stable and reliable method, CNV-Seq can accurately detect the MECP2 duplication syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread and poses a major threat to public health worldwide. The whole genome sequencing plays a crucial role in virus surveillance and evolutionary analysis. In this study, five genome sequences of SARS-CoV-2 were obtained from nasopharyngeal swab samples from Zhengzhou, China. Following RNA extraction and cDNA synthesis, multiplex PCR was performed with two primer pools to produce the overlapped amplicons of ~1,200 bp. The viral genomes were obtained with 96% coverage using nanopore sequencing. Forty-five missense nucleotide mutations were identified; out of these, 5 mutations located at Nsp2, Nsp3, Nsp14, and ORF10 genes occurred with a

The rapid spread of pneumonia caused by SARS-CoV-2 has seriously threatened people. In this study, we detected the expression of anti-SARS-CoV-2 IgG/IgM and respiratory tract SARS-CoV-2 RNA in patients with COVID-19 and explored the correlation and clinical significance between SARS-CoV-2 antibody and respiratory SARS-CoV-2 RNA.From March 5, 2020 to April 28, 2020, 48 cases with COVID-19 diagnosed in Beijing Xiaotangshan Hospital were enrolled. SARS-CoV-2 RNAs were detected by real-time fluorescence RT-PCR method. Serum SARS-CoV-2 IgG/IgM antibodies were determined by colloidal gold immunochromatography. The statistical analysis was performed using chi-squared test.In all the patients, SARS-CoV-2 RNA among 270 upper respiratory tract (nasal or throat swabs) samples, 71 lower respiratory tract (sputum) samples, and anti-SARS-CoV-2 IgM/IgG antibodies in 123 serum samples were detected during the hospitalization period. The positive rate of anti-SARS-CoV-2 IgG was significantly higher than that of anti-SARS-CoV-2 IgM within the first week after symptom onset (p0.05). The positive rate of anti-SARS-CoV-2 IgG was also significantly higher than that of anti-SARS-CoV-2 IgM during day 8 - 30 after symptom onset (p0.01). The positive rate of SARS-CoV-2 RNA in the lower respiratory tract specimens (64.8%, 46/71) was significantly higher than that in the upper respiratory tract (46.7%, 126/270) (p0.05). The positive rate (100%, 4/4) of SARS-CoV-2 RNA detection in the lower respiratory tract specimens before IgG seroconversion was significantly higher than that of the positive rate (59.3%, 32/54) after IgG seroconversion (p0.01). The positive rate (72.2%, 57/79) of SARS-CoV-2 RNA detection in the upper respiratory tract specimens before IgG seroconversion was significantly higher than that of the positive rate (30.7%, 39/127) after IgG seroconversion (p0.01).Anti-SARS-CoV-2 IgG might be detected within the first week after symptom onset. The application of SARS-CoV-2 antibody (IgG/IgM) detection is important for the suspected cases of SARS-CoV-2 infection with negative SARS-CoV-2 RNA results. The positive rate of SARS-CoV-2 RNA detection in the lower respiratory tract specimens was significantly higher than that in the upper respiratory tract. Sputum detection is recommended for the detection of SARS-CoV-2 RNA. Using lower respiratory tract specimens may reduce the false negative PCR tests. The detection of SARS-CoV-2 RNA can be improved by investigating follow-up specimens over time.

This article describes a technique for making an esthetic treatment plan by using a virtual face scan reconstructed from digital photographs through three-dimensional dense face alignment (3DDFA) and intraoral scans. Portrait photographs were captured with a digital camera and were reconstructed to a virtual 3D face scan by 3DDFA. After scaling the virtual face scan to the correct size, intraoral scans and virtual face scans were aligned to create a 3D view of the patient. A virtual diagnostic waxing was created accordingly. In select cases, this technique can provide 3D esthetic predictions when 3D face imaging devices are not available.

To evaluate the efficacy and safety of resveratrol combined with ablative fractional COThirty-two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period.All subjects in TG achieved improvements of their photoaging signs compared to pre-treatment both the laser side and the non-laser side at 6 months (p 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p 0.05). On the non-laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG.The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.

BACKGROUND Actinic keratosis (AK) is a precancerous disease, caused by ultraviolet radiation (UV). OBJECTIVE To analyze the clinical and pathological characteristics of AK in four areas with different ultraviolet radiation intensities. METHODS 1188 diagnosed AK patients, from January 2000 to July 2015, in dermatology department of four hospitals were collected. The UV intensity of hospital located cities from high to low is Kunming, Yinchuan, Shenyang and Nanjing. The information comes from medical records, and the pathological types and Keratinocyte Intraepithelial Neoplasia (KIN) grades were checked by two experienced pathologists. All information was conducted a retrospective multicenter research. RESULTS The patients were mainly middle-aged and elderly female, which was in direct contrast to the majority of men in European. The age of onset in Kunming group was lower than that in Yinchuan Group (p = 0.013) and Nanjing Group (p

To analyze the prenatal diagnosis, parental verification and pregnancy outcome of 6 fetuses with 22q11.2 microdeletion syndrome.Copy number variation sequencing (CNV-seq)and chromosomal microarray analysis (CMA) were carried out for the fetuses.The fetuses were found to harbor 2.54-3.2 Mb microdeletions of the 22q11.2 region, among which one was maternally inherited and one was paternally inherited. Two parents opted to continue with the pregnancy, and 4 chose induced labor. One fetus was found to have tetralogy of Fallot, while two carrier parents and one fetus appeared to have normal phenotype.22q11.2 microdeletions identified upon prenatal diagnosis should be treated carefully, with ultrasonic scan and parental verification taken into account.

This study evaluated the difference in treatment response and survival profiles between drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) treatments in Chinese hepatocellular carcinoma (HCC) patients. A total of 120 HCC patients were consecutively enrolled in this prospective cohort study, which showed that DEB-TACE achieved higher complete response (CR) (30.8%) compared with cTACE (7.4%) with no difference in overall response rate (ORR) for patients treated with DEB-TACE and cTACE (80.8% vs. 73.5%). In addition, DEB-TACE was associated with a lower rate of progressive disease (PD) compared with cTACE (1.9% vs. 11.8%). With respect to survival, patients in the DEB-TACE group achieved median progression-free survival (PFS) of 15 months (95% CI 12‐18 months), which was longer than the cTACE group [median PFS 11 months (95% CI 10‐12 months)]. Median overall survival (OS) was also longer with DEB-TACE [25 months (95% CI 22-28 months)] when compared with cTACE [21 months (95% CI 18‐24 months)]. Univariate and multivariate logistic regression analysis showed that DEB-TACE was an independent predictive factor for achieving CR. Univariate Cox’s regression analysis revealed that DEB-TACE was a predictive factor for prolonged PFS and OS, while multivariate analysis demonstrated that DEB-TACE was not an independent factor for predicting PFS or OS. In conclusion, we found that DEB-TACE achieved higher treatment response and prolonged survival compared with cTACE in Chinese HCC patients.

Summary Background Melasma is an acquired, common hyperpigmented disorder on the face. While many therapeutic approaches are available, their efficacy is moderate. Objective To investigate the safety and efficacy of a cream containing herbal mixture for melasma. Methods A total of 90 volunteers with melasma were enrolled in this randomized, double‐blind, controlled clinical study, and they were randomly divided into three groups (A, B, and C). Patients in group A were treated with a cream containing herbal mixture, while groups B and C were treated with arbutin cream and placebo, respectively, twice daily for 12 weeks. Melasma area and severity index (MASI) score, melanin index (MI), erythema index (EI), changes in density of inflammatory cells, and adverse events were evaluated every 4 weeks. Results Although MASI scores declined significantly in both groups A and B (P

The limitations in discriminating preablation disease-active status of differentiated thyroid carcinoma (DTC) still represent a major challenge to radioiodine dose management. Cytokines, the small protein signaling molecules that constitute the thyroid tumor microenvironment, play significant roles in the facilitation of intercellular communication and the control of tumorigenesis. Also, more attention should be paid to the molecular events within the innate and adaptive immune systems that occur after the organism being exposed to ionizing radiation. Therefore, we implemented a study of 260 patients with DTC in thyroid hormone withdrawal status who were treated with total thyroidectomy to explore the relationship between cytokines and recurrence/active disease status. Besides, we made a cross-sectional study to analyze pre- and post-ablation serum concentration of cytokines of 86 patients with DTC. There was a relationship between clinicohistopathological characteristics of patients with DTC and the presence of cytokines. It is noteworthy that patients with recurrence/active disease were at a higher serum interleukin-2 receptor (IL-2R) level than the disease-free patients (213.59 ± 75.43 pg/ml vs. 186.80 ± 77.40 pg/ml, P = 0.005). Positive correlation was observed between serum IL-2R and thyroglobulin (Tg) (P = 0.003). We also found significant changes in the cytokine profile after radioiodine ablation, including the decrease of tumor necrosis factor-α and IL-8 (P < 0.001, P < 0.001, respectively), and increase of IL-2R (P < 0.001). Thus, we suggest that serum IL-2R may assist in evaluating the disease status during the post-thyroidectomy follow-up and radioiodine therapy has an immunoregulatory effect on serum cytokines.

BackgroundPolyploid species often originate recurrently. While this is well known, there is little information on the extent to which distinct allotetraploid species formed from the same parent species differ in gene expression. The tetraploid yarrow speciesAchillea alpinaandA. wilsonianaarose independently from allopolyploidization between diploidA. acuminataandA. asiatica. The genetics and geography of these origins are clear from previous studies, providing a solid basis for comparing gene expression patterns of sibling allopolyploid species that arose independently.ResultsWe conducted comparative RNA-sequencing analyses on the twoAchilleatetraploid species and their diploid progenitors to evaluate: 1) species-specific gene expression and coexpression across the four species; 2) patterns of inheritance of parental gene expression; 3) parental contributions to gene expression in the allotetraploid species, and homeolog expression bias. DiploidA. asiaticashowed a higher contribution than diploidA. acuminatato the transcriptomes of both tetraploids and also greater homeolog bias in these transcriptomes, possibly reflecting a maternal effect. Comparing expressed genes in the two allotetraploids, we found expression of ca. 30% genes were species-specific in each, which were most enriched for GO terms pertaining to “defense response”. Despite species-specific and differentially expressed genes between the two allotetraploids, they display similar transcriptome changes in comparison to their diploid progenitors.ConclusionTwo independently originatedAchilleaallotetraploid species exhibited difference in gene expression, some of which must be related to differential adaptation during their post-speciation evolution. On the other hand, they showed similar expression profiles when compared to their progenitors. This similarity might be expected when pairs of merged diploid genomes in tetraploids are similar, as is the case in these two particular allotetraploids.

To analyze the clinical phenotype and genetic variants in five Chinese pedigrees affected with Dysferlinopathy.Next generation sequencing (NGS) was carried out for the probands from the five pedigrees. Suspected variants were validated by Sanger sequencing. Pathogenicity of the variants was assessed based on the standards and guidelines by the American College of Medical Genetics and Genomics (ACMG).Ten DYSF gene variants (including 5 frameshift variants, 3 splicing variants, 1 missense variant and 1 nonsense variant) were detected. Among these, c.1375dupA (p.Met459Asnfs*15), c.610CT (p.Arg204X), c.1180+5GA and c.1284+2TC were known to be pathogenic, while c.4008_4010delCCTinsAC (p.Leu1337Argfs*8), c.1137_1169del (p.379_390del), c.754AG(p.Thr252Ala), c.1175_1176insGCAGAGTG (p.Met394Serfs*7), c.3114_3115insCGGC (p.Arg1040Profs*74) and c.1053+3GC were unreported previously. Of the six novel variants, c.1137_1169del, c.1175_1176insGCAGAGTG and c.3114_3115insCGGC were predicted as pathogenic (PVS1+PM2+PM3), c.4008_4010delCCTinsAC as likely pathogenic (PVS1+PM2), c.754AG and c.1053+3GC as variants of uncertain significance based on the ACMG standards and guidelines.Variants of the DYSF gene probably underlay Dysferlinopathy in the patients among the five pedigrees. Above finding has enriched the spectrum of DYSF gene variants.

BackgroundPemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases.PurposeTo investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients.MethodsAntibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies.Results98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml.ConclusionPemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.

Background The purpose of this study is to investigate and analyze the prevalence and influencing factors of stroke in hypertensive patients aged 60 and above in Jiading District, Shanghai. Methods The population-based study included 18,724 screened people with hypertension (age ≥ 60 years, 48.7% women). From 2016 to 2019, data on demographics, potential influencing factors and health status were collected through face-to-face interviews, physical examinations, and laboratory tests. Logistic multivariate logistic regression model was used to analyze the influencing factors associated with stroke. Results Among the object of study from 2016 to 2019, 2,025 patients were screened for stroke, with the overall prevalence rate of 10.82% (10.41%-11.23%). Multivariate adjusted model analysis showed that dyslipidemia (OR:1.31,95%CI:1.19–1.45), lack of exercise (OR:1.91,95%CI:1.32–2.76), atrial fibrillation [OR:1.49,95%CI:1.35–1.65), family history of stroke (OR:2.18,95%CI:1.6–2.88) were the significant independent influencing factors of stroke in hypertensive patients over 60 years old. When these four factors were combined, compared with participants without any of these factors, the multi-adjusted odds ratios (95% confidence interval) of risk of stroke for persons concurrently having one, two and three or more of these factors were 1.89 (1.67–2.13), 2.15 (1.86–2.47) and 6.84 (4.90–9.55), respectively (linear trend P < 0.001); after multivariate adjustment, the family history of stroke had additive interaction with lack of exercise [RERI = 1.08(0.22–1.94), AP = 0.19(0.04–0.35), S = 1.31(1.02–1.69)], dyslipidemia [RERI = 0.87(0.41–1.33), AP = 0.23(0.08–0.38), S = 1.46(1.04–2.05)]. Conclusion The prevalence of stroke was high in hypertensive patients aged 60 and above in Jiading District, Shanghai. Dyslipidemia, lack of exercise, atrial fibrillation and family history of stroke were significantly associated with stroke in hypertensive population. Stroke risk can be increased especially when multiple factors coexisting, and family history of stroke combined with a lack of exercise or dyslipidemia.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is an extremely rare subtype of primary cutaneous T cell lymphomas mimicking panniculitis. Clinically, patients are usually presented with subcutaneous nodules, which usually leads to initial misdiagnosis as a benign cutaneous condition. Here, we report a 40-year-old female who presented with subcutaneous erythematous nodules on her extremities with fever. On the basis of the clinical presentations, histopathological features and immunohistochemical findings, a diagnosis of SPTCL was made. The patient was treated with the injection of recombinant human interferon α-1b (30 μg) every other day for 3 months. The lesions gradually regressed. No new erythema nodules reappeared during the 10-month follow-up.

BACKGROUND There is an increasing demand for fat reduction and body contouring procedures. Noninvasive radiofrequency devices have been used to tighten skin and treat cellulite, but there are few studies confirming their efficacy for abdominal fat reduction. OBJECTIVE This study explored the effects of four noninvasive radiofrequency (RF) treatments on abdominal fat in Asian subjects, evaluating body weight, body mass index (BMI), and waist circumference. METHODS In this study, 16 patients with abdominal obesity were treated four times with a noninvasive and contactless selective RF device (VANQUISH ME™, BTL Aesthetics). Treatments were 7 days apart and lasted 45 min each. The BMI and circumference of the upper, middle, and lower abdomen were measured at baseline and after each treatment. RESULTS There were statistically significant reductions in BMI and abdominal circumference in all 16 patients (P

Background Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD. Methods The gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis. Results Among 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P Conclusion We successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.

To develop and validate a preoperative CT-based nomogram combined with radiomic and clinical-radiological signatures to distinguish preinvasive lesions from pulmonary invasive lesions.This was a retrospective, diagnostic study conducted from August 1, 2018, to May 1, 2020, at three centers. Patients with a solitary pulmonary nodule were enrolled in the GDPH center and were divided into two groups (7:3) randomly: development (n = 149) and internal validation (n = 54). The SYSMH center and the ZSLC Center formed an external validation cohort of 170 patients. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to feature signatures and transform them into models.The study comprised 373 individuals from three independent centers (female: 225/373, 60.3%; median [IQR] age, 57.0 [48.0-65.0] years). The AUCs for the combined radiomic signature selected from the nodular area and the perinodular area were 0.93, 0.91, and 0.90 in the three cohorts. The nomogram combining the clinical and combined radiomic signatures could accurately predict interstitial invasion in patients with a solitary pulmonary nodule (AUC, 0.94, 0.90, 0.92) in the three cohorts, respectively. The radiomic nomogram outperformed any clinical or radiomic signature in terms of clinical predictive abilities, according to a decision curve analysis and the Akaike information criteria.This study demonstrated that a nomogram constructed by identified clinical-radiological signatures and combined radiomic signatures has the potential to precisely predict pathology invasiveness.• The radiomic signature from the perinodular area has the potential to predict pathology invasiveness of the solitary pulmonary nodule. • The new radiomic nomogram was useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection in patients with early-stage non-small-cell lung cancer.

Healing after mammalian skin injury involves the interaction between numerous cellular constituents and regulatory factors, which together form three overlapping phases: an inflammatory response, a proliferation phase and a remodelling phase. Any slight variation in these three stages can substantially alter the healing process and resultant production of scars. Of particular significance are the mechanisms responsible for the scar‐free phenomenon observed in the foetus. Uncovering such mechanisms would offer great expectations in the treatment of scars and therefore represents an important area of investigation. In this review, we provide a comprehensive summary of studies on injury‐induced skin regeneration within the foetus. The information contained in these studies provides an opportunity for new insights into the treatment of clinical scars based on the cellular and molecular processes involved., The schematic diagram shows the distinction between the healing process of the foetus and the adult mice after injury: the foetus of E16 shows less inflammatory cell infiltration, fibroblast colonization and ECM deposition than the adult mice. In addition, the participation of proteins and non‐coding RNAs (miRNAs, lncRNAs) also plays a key role in different prognosis.

To detect genomic copy number variations (CNVs) among 145 children with unexplained mental retardation/developmental delay (MR/DD) by using low-depth whole-genome copy number variation sequencing (CNV-seq).Peripheral blood samples were collected from the patients and subjected to DNA extraction and CNV-seq. The results were analyzed by a combination of bioinformatic tools.Forty-nine patients were found to carry a total of 67 CNVs with an average size of 5.27 Mb. Among these, 22 patients were assessed to carry MR/DD-related CNVs involving 21 syndromes. This gave a diagnostic rate of 15.17%(22/145) for CNVs associated with unexplained MR/DD. The corresponding regions of the 22 MR/DD-related CNVs in the human genome covered 174 MR/DD-related pathogenic genes, which have mapped to 18 sections on 10 chromosomes.Genomic CNVs-related microdeletions/duplications account for a significant proportion of unexplained MR/DD, for which CNV-seq can provide an accurate diagnosis.

Despite great progress in nitric oxide (NO) controlled releasing strategies, the in vivo spatiotemporal NO distribution of arteries is still unclear, which makes it impossible to assess the status of arteries and render NO-based therapies in vivo largely fruitless. Here, we presented personalized computational modelling to calculate the NO distribution on the endothelial surface and in the arterial wall of human atherosclerotic carotid artery bifurcations using models constructed from MRI. The computational results indicated the distribution of NO in the atherosclerotic artery is highly uneven. The volume-weighted average NO concentration (CV) in regions with lipid plaques (9.76 ± 2.82 nM) was about 22 times higher than that in the plaque-free regions. Regions where also the calcified plaque components and the intraplaque hemorrhages are present would increase and abate the CV, respectively. The dynamic blood flow during the cycle would directly affect the distribution of NO on the endothelial surface. The luminal NO distribution is closely related to hemodynamic indicators, including wall shear stress (WSS), time averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT). In conclusion, atherosclerotic components determine the space-averaged NO concentration in arterial wall and blood flow controls the luminal NO concentration.

Infraorbital dark circles (DC) are defined as a symptom that presents darkness under infraorbital eyelids. The objective of this study was to evaluate the efficacy and safety of nano-microneedle-assisted phenylethyl resorcinol (PR) for the treatment of infraorbital dark circles.Twenty female participants were randomized to two groups. In the experimental group (group E), participants received topical PR gel under the left orbit once a day and topical plus nano-microneedle-assisted PR gel under the right orbit twice a week. In the control group (group C), participants were treated with gel without PR. Melanin index (MI) and erythema index (EI) were measured before the session (T0), 4 and 8 weeks during the treatment session (T4, T8), and 1 and 2 months after the last session (T12, T16). The global assessment was performed by a blinded dermatologist.The mean value of MI in group E was significantly lower than the baseline at T8 (P .05), and the right side decreased more significantly than the left side (P .05). However, there was no difference of MI before and after treatment in group C (P .05). There was no big difference of the mean EI between the two sides (P .05). The treatment was well tolerated, and no serious adverse effects were reported.PR combined with nano-microneedle could be an effective and safe method for infraorbital DC.

Symptomatic dermographism (SD) is the most common form of physical urticaria. So far no promising serum biomarkers for SD have been reported. Recently, microRNAs (miRNAs) have been reported to be serum biomarkers for chronic spontaneous urticaria. However, association of miRNAs with SD remains unclear. We enrolled 55 SD patients and 52 healthy controls in this study. We found that serum expressions of miR-126-3p and miR-16-5p were significantly downregulated in active SD patients and upregulated in remission. The area under the curve values of miR-126-3p (0.769) and miR-16-5p (0.789) showed significant ability to diagnostic SD. Serum level of vascular endothelial growth factor (VEGF)-A, a known target of the two miRNAs, was significantly increased in active SD patients and decreased in remission. Moreover, serum VEGF-A level was inversely correlated with expressions of miR-126-3p and miR-16-5p. Our findings indicate that miR-126-3p and miR-16-5p can serve as potential serum biomarkers for SD.

To evaluate the relationship between the network metrics of 68 brain regions and duration of temporal lobe epilepsy (TLE). Magnetoencephalography (MEG) data from 53 patients with TLE (28 left TLE, 25 right TLE) were recorded between seizures at resting state and analyzed in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and lower gamma (30-48 Hz). Three local network metrics, betweenness centrality, nodal degree, and nodal efficiency, were chosen to analyze the functional brain network. In Left, Right, and All (Left + Right) TLE groups, different metrics provide significant positive or negative correlations with the duration of TLE, in different frequency bands, and in different brain regions. In the Left TLE group, significant correlation between TLE duration and metric exists in the delta, beta, or lower gamma band, with network betweenness centrality, nodal degree, or nodal efficiency, in left caudal middle frontal, left middle temporal, or left supramarginal. In the Right TLE group, significant correlation exists in lower gamma or delta band, with nodal degree, or nodal efficiency, in left precuneus or right temporal pole. In the All TLE group, the significant correlation exists in delta, theta, beta, or lower gamma band, with nodal degree, or betweenness centrality, in either left or right hemisphere. Network metrics for some specific brain regions changed in patients with TLE as the duration of their TLE increased. Further researching these changes may be important for studying the pathogenesis, presurgical evaluation, and clinical treatment of long-term TLE.

Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 μM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 μg mL-1) and GA (50 μM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 μg mL-1) and GA (50 μM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

INTRODUCTION: Reactive carbonyl species including methylglyoxal (MGO) are oxidation metabolites of glucose and precursors of advanced glycation end products (AGEs). They are important mediators of cellular oxidative stress and exacerbate skin complications. Published data supports that certain phenolic compounds can exert cellular protective effects by their antioxidant activity. A phenolic-enriched maple syrup extract (MSX) was previously reported to show protective effects against AGEs- and MGO-induced cytotoxicity in human colon cells but its skin protective effects remain unknown. OBJECTIVE: The protective effects of MSX were evaluated against hydrogen peroxide (H(2)O(2))- and MGO-induced cytotoxicity in human keratinocytes (HaCaT cells). METHODS: Cellular viability and antioxidant activity were evaluated by the luminescent cell viability CellTiter-Glo® assay and the reactive oxygen species (ROS) assay, respectively. A single-cell gel electrophoresis (Comet assay) was used to measure the strand breaks in the DNA of HaCaT cells. RESULTS: MSX (at 50 μg/mL) ameliorated H(2)O(2)- and MGO-induced cytotoxicity by increasing cell viability by 21.5 and 25.9%, respectively. MSX reduced H(2)O(2)- and MGO-induced ROS production by 69.4 and 56.6%, respectively. MSX also reduced MGO-induced DNA damage by 47.5%. CONCLUSION: MSX showed protective effects against H(2)O(2)- and MGO-induced cytotoxicity in HaCaT cells supporting its potential for dermatological and/or cosmeceutical applications.

Background. Bullous pemphigoid (BP) is a common T helper 2- (Th2-) dominated autoimmune blistering skin disease with significant mortality. MicroRNAs (miRNAs), which are endogenous noncoding RNA molecules, have been reported to be potential biomarkers for some autoimmune diseases; however, to date, there exist no reports on serum expression profiles of miRNAs in BP patients. Methods. A RNA quantitative PCR- (qPCR-) based array was conducted on sera from 20 active BP patients and 20 healthy controls for screening of miRNAs. Significantly dysregulated miRNAs were validated with use of qPCR as performed on sera samples of 45 active BP patients and 60 healthy controls. Serum CCL17, anti-BP180, and anti-BP230 levels were measured with use of ELISA. Results. Relative baseline expression levels of serum miR-1291 were significantly upregulated in the 45 BP patients as compared with the 60 healthy controls (P<0.001) and significantly decreased in the disease control stage (n=13, P=0.006). In addition, these baseline miR-1291 levels showed a significant positive correlation with the baseline levels of serum CCL17 (P<0.001) and anti-BP180 (n=38, P=0.024). Like that observed for miR-1291, baseline levels of serum CCL17 were also significantly elevated in the 45 BP patients compared with the 60 healthy controls (P<0.001) and significantly decreased in the disease control stage (n=13, P=0.002). However, for anti-BP180, baseline serum levels were significantly elevated in only 38 of the 45 BP patients and significantly decreased in the disease control stage (n=10, P=0.004). Conclusions. Relative expression levels of serum miR-1291 can reflect disease activity of BP. miR-1291 may function as an important new serum biomarker for BP.

Background. Currently, effective genetic markers are limited to predict the clinical outcome of melanoma. High-throughput multiomics sequencing data have provided a valuable approach for the identification of genes associated with cancer prognosis. Method. The multidimensional data of melanoma patients, including clinical, genomic, and transcriptomic data, were obtained from The Cancer Genome Atlas (TCGA). These samples were then randomly divided into two groups, one for training dataset and the other for validation dataset. In order to select reliable biomarkers, we screened prognosis-related genes, copy number variation genes, and SNP variation genes and integrated these genes to further select features using random forests in the training dataset. We screened for robust biomarkers and established a gene-related prognostic model. Finally, we verified the selected biomarkers in the test sets (GSE19234 and GSE65904) and on clinical samples extracted from melanoma patients using qRT-PCR and immunohistochemistry analysis. Results. We obtained 1569 prognostic-related genes and 1101 copy-amplification, 1093 copy-deletions, and 92 significant mutations in genomic variants. These genomic variant genes were closely related to the development of tumors and genes that integrate genomic variation. A total of 141 candidate genes were obtained from prognosis-related genes. Six characteristic genes (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) were selected by random forest feature selection, many of which have been reported to be associated with tumor progression. Cox regression analysis was used to establish a 6-gene signature. Experimental verification with qRT-PCR and immunohistochemical staining proved that these selected genes were indeed expressed at a significantly higher level compared with the normal tissues. This signature comprised an independent prognostic factor for melanoma patients. Conclusions. We constructed a 6-gene signature (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) as a novel prognostic marker for predicting the survival of melanoma patients.

Background Extramammary Paget’s disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD. Methods Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 healthy volunteers were enrolled in this study. Serum from all of subjects were collected to identify miRNAs (by miRNA array global normalization, RT-PCR validation, and receiver operating characteristic curve analysis) that could be potential diagnostic markers for EMPD. Results The miRNA array analyses revealed that the expressions of 37 miRNAs from the EMPD patients were different (change ≥4-fold) from health volunteers. Among these miRNAs, the expression of miR-155 was significantly increased (p

On October 25, 2018, the National Health Commission of China issued the National Essential Medicines List (2018 edition) [NEML (2018)]. The NEML (2018) contains 685 drugs, which consist of 417 chemicals and biological products and 268 Chinese patent medicines. Compared to the 2012 version of the NEML, a total number of 165 drugs were added, representing an increase of 31.7%. The biggest increase (90.9%) is in Chinese patent medicines for surgical use. The NEML (2018) set up the category of pediatric medications for the first time, and 11 cancer drugs were added. The NEML (2018) is characterized by: "basic" to "comprehensive" coverage, it includes both Chinese and Western medicines, it now includes pediatric drugs, and more cancer drugs have been added. There are several issues with the new NEML such as the link between the essential medicines system and the medical insurance system and establishment of firm support for implementation.

Background Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. Objectives To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. Methods HaCaT cells were subjected to 44 °C (compared to 37 °C) waterbath for 30 min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. Results DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB, 3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α 4 ; IL-1B, 5 TNFAIP3 6 and IL-8 7 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. Conclusions Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.