ObjectiveTo explore the key molecules regulated by norcantharidin (NCTD) in colon cancer treatment.MethodsWe used cell counting kit-8 and 5-ethnyl-2′-deoxyuridine/Hoechst staining assays to study the effects of NCTD on cell proliferation in colon cancer. Annexin V-fluorescein isothiocyanate/propidium iodide staining was used to evaluate apoptosis, whereas Transwell assays were conducted to evaluate migration and invasion. We performed RNA sequencing to analyze the changes in gene expression after treatment. Differential analysis was performed using differential expression sequencing 2 (Deseq2) in R. Cytoscape was used to construct a competing endogenous RNA (ceRNA) network and Gene Expression Omnibus (GEO) datasets were used to validate sine oculis homeobox homolog 4 (SIX4) expression in colon cancer tissues. Furthermore, the prognostic potential of SIX4 was evaluated using receiver-operating characteristic curves. We conducted an immune infiltration analysis to explore the SIX4 relationship with the immune microenvironment in colon cancer. Finally, SIX4 expression, pan-cancer prognosis, tumor mutation burden (TMB) correlations, microsatellite instability (MSI), and mismatch repair (MMR) were analyzed.ResultsNCTD inhibited colon cancer cell proliferation (P .0001), induced apoptosis (P = .0007), and suppressed the migration and invasion of colon cancer cells. The H19/miR-193b-3p/SIX4 axis was identified as the key ceRNA network involved in the anticancer activity of NCTD. SIX4 is highly expressed in colon cancer tissues, shortening patient survival and affecting immune infiltration. A pan-cancer analysis showed that SIX4 overexpression affects the survival of various cancers. Finally, we correlated SIX4 expression with TMB, MSI, and MMR expression.ConclusionNCTD inhibits the malignant behaviour of colon cancer cells. SIX4 is abnormally expressed in multiple tumor types, significantly affecting the overall survival of patients with cancer, and is a core regulatory target of NCTD in the treatment of colon cancer.

Objective To explore whether the phosphorylation of NF-κB P65 subunit is involved in the cytotoxicity to and inflammation in an immortal human keratinocyte cell line HaCaT during cobalt chloride (CoCl2-induced chemical hypoxia. Methods HaCaT cells were treated with CoCl2 of 2 mmol/L to set up a chemical hypoxia-induced cell model of injury. Then, RNA interference was used to down-regulate the expression of P65 in CoCl2-induced HaCaT cells. After additional culture, cell viability was tested by cell counting kit8 (CCK-8), the levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) were detected by ELISA kits, phosphorylated and total P65 protein was measured by Western blot. Results The exposure of HaCaT cells to 2 mmol/L CoCl2 for 0 to 4 hours enhanced the phosphorylation of P65, which began at 0.5 hour, peaked at 1.5 hours, and restored to the normal level at 4 hours, and the level of P65 phosphorylation was about 6.6 times that in the untreated control group. The CoCl2 of 2 mmol/L decreased the cell viability of HaCaT cells in a time dependent manner, and a significant difference was observed in the viability of HaCaT cells between CoCl2-treated and untreated HaCaT cells at 2, 4, and 6 hours (P ＜ 0.05, 0.01, 0.01 ). The release of IL-6 and IL-8 from HaCaT cells was also promoted by CoCl2 treatment. The knockdown of P65 expression with siRNA markedly suppressed the CoCl2-induced cytotoxicity to and increase in the release of IL-6 and IL-8 from HaCaT cells,despite of an increment in cell viability by about 11%. Conclusion The phosphorylated P65 subunit mediates CoCl2-induced cytotoxicity and inflammatory injury to HaCaT cells.

ObjectiveTo compare the efficacy and tolerability of 1-week 1％ terbinafine hydrochloride cream, 1- and 4-week 2％ miconazole nitrate cream in the treatment of interdigital tinea pedis, and to observe the relapse in patients treated with these regimens. MethodsA multi-center, randomized, double-blind and parallel group study was conducted. By using a stratified randomization protocol, patients were divided into 3 groups to apply terbinafine cream twice daily for 1 week and inert cream(placebo) for the next 3 weeks (1week terbinafine group), miconazole cream twice daily for 1 week and inert cream(placebo) for the next 3 weeks (1-week miconazole group), and miconazole cream twice daily for 4 weeks (4-week miconazole group),respectively. Clinical and mycological assessment was made on week 1, 3, 4, 6, 9 and 12 after the initiation of treatment. ResultsA total of 152 patients with positive baseline mycological culture were eligible for the efficacy analysis. After 4-week treatment, the mycological cure rates were 94.7％, 87.8％ and 82.6％, global effective rates 89.5％, 81.6％ and 63.0％, respectively for the 1-week terbinafine group, 4-week miconazole group and 1-week miconazole group. On week 12, the mycological relapse rates in 1-week terbinafine, 4-week miconazole and 1-week miconazole group were 13％, 14％ and 21％ respectively, and the incidence of adverse reaction was 2.38％, 2.38％ and 3.57％, respectively. ConclusionsAs far as the efficacy and recurrence in patients are concerned, the 1-week terbinafine cream regimen is similar to the 4-week miconazole cream regimen for the treatment of interdigital tinea pedis.

Objective To estimate the influences of N-acetyl cysteine (NAC) on a chemical hypoxiamimetic agent CoCl2 induced-injury to, and expressions of inflammatory factors by, an immortal human skin keratinocyte line HaCaT. Methods HaCaT cells were treated with CoCl2 of 2000 μmol/L for 4 hours to set up a chemical hypoxia-induced cell model of skin injury. NAC of various concentrations ( 1000, 2000, 3000 μmol/L)was used to pretreat HaCaT cells for 2 hours prior to the establishment of cell model. After these treatments,cell viability was detected by cell counting kit 8 (CCK-8), the levels of interleukin 6 and 8 (IL-6 and -8) and tumor necrosis factor α (TNF-α) in culture supernatant by ELISA kits, mitochondrial membrane potential (MMP) by rhodamine 123 (Rh123) staining and photofluorography, intracellular reduced glutathione (GSH)content by glutathione detection kit. Results An obvious decline was observed in HaCaT cell viability after pretreatment with various concentrations of NAC for 2 hours. The treatment with CoCl2 of 2000 μmol/L for 4 hours induced an elevation in the supernatant levels of IL-6, IL-8 and TNF-α and a decrease in GSH content and MMP, while the pretreatment with NAC for 2 hours retarded the CoCl2-induced increase in IL-6 and IL-8 levels as well as decrease in GSH content and MMP. Conclusion The reactive oxygen species (ROS) scavenger NAC can protect against CoCl2-induced injury to and inflammatory reaction in HaCaT cells, which may be associated with a decrement in oxidative stress.

Objective To observe the clinical efficacy and safety of5%imiquimod cream in the top-ical treatment of condyloma acuminatum(CA).Methods A randomized,double-blind,parallel placebo-controlled clinical study was conducted.The test drug was topically used in CA patients,three times a week for8weeks.Patients whose warts cleared completely were followed up for one month to determine recurrence rates.Results Two hundred fifty-eight patients with anogenital warts were enrolled into this trial.One hun-dred twenty-nine patients were randomly selected to receive5%imiquimod cream;129patients were ran-domly chosen to receive placebo cream.Results showed that the cure rates were12.30%,32.79%,50%,60.66%respectively in study group for2,4,6,8weeks and were4.88%,14.63%,19.51%,26.02%respec-tively in control group for2,4,6,8weeks(P

Objective To investigate the colonization features of Staphylococcus aureus (S. aureus) in the skin lesions of eczema and atopic dermatitis (AD), and to evaluate the therapeutic effect of combination topical treatment with mupirocin and hydrocortisone butyrate. Methods A multicentre, double-blind randomi-zed trial was conducted. The SCORAD was evaluated on day 1, 7, 14 and 28. Swabs for bacterial isolation were taken from the lesional skin and non-lesional skin. A combination topical therapy with mupirocin ointment and hydrocortisone butyrate ointment was used in treatment group, with vehicle ointment and hydrocortisone butyrate ointment as a control. Results Three hundred and twenty seven patients were enrolled in the study, including 208 patients with eczema and 119 patients with atopic dermatitis. Bacteria were isolated from 70.19% of lesional skin and 32.69% of non-lesional skin of patients with eczema, in which S. aureus accounted for 47.26% and 27.94% respectively. Bacteria were isolated from 74.79% of the lesional skin and 34.45% of non-lesional skin of patients with atopic dermatitis, in which S. aureus accounted and 79.78% or 80.49% respectively. The amount of S. aureus colonized was markedly higher in the lesional skin than that in non-lesional skin, either in eczema patients or in atopic dermatitis (P 0.05). Conclusions The bacterial colonization, especially S. aureus, is more frequently dectected in the lesional skin of eczema patients and AD patients than that in the non-lesional skin, which may be related in the pathogenesis of eczema and AD. And, early application of combination therapy with topical antibiotics and corticosteroids is beneficial to the patients.

Objective To observe the clinical efficacy and safety of 5% imiquimod cream in topical treatment of anogenital warts. Methods A randomized, double-blind, parallel placebo-controlled clinical study was conducted. Patients with anogenital warts were instructed to apply the test drug topically and then clean the drug with water 6 ~ 8 hours later, three times a week for 8 weeks. Patients whose warts cleared completely were followed up for one month to determine recurrence rates. Results Two hundred and thirty-one patients with anogenital warts were enrolled in this trial. One hundred and sixteen patients were randomly selected to receive 5% imiquimod cream; and the other receive placebo cream. For 2, 4, 6, 8 weeks, the cure rates were 8.41%, 30.84%, 49.53%, 61.68%, respectively in the study group, and 2.68%, 7.14%, 16.07%, 24.11%, respectively in the control group (P

Objectives To study the role of interleukin-4 (IL-4) and interferon-gamma (IFN-?) in the pathogenesis of atopic dermatitis and eczema,and the changes of serum levels of IL-4 and INF-? with topical treatment of co rticosteroid plus antibiotic cream or corticosteroid cream alone.Methods Seru m levels of IL-4 and IFN-? were detected by enzyme-linked immunosorbent assa y(ELISA).Results Serum levels of IL-4 and INF-? were significantly higher in the patients with atopic dermatitis and eczema than those in the normal control s,respectively(both P

Aim To explore the effect of chemical hypoxia-mimetic agent,cobalt chloride(CoCl2)on inflammatory reaction in human keratinocytes(HaCat cells).Methods After HaCat cells were treated with CoCl2 at different concentrations to set up a chemical hypoxia-induced cell model of skin injury,cell viability,intracellular reactive oxygen species(ROS),mitochondrial membrane potential(MMP),the levels of both interleukin 6(IL-6)and interleukin 8(IL-8)as well as the expression of heme oxygenase-1(HO-1)were detected.Results The viability of HaCat cells was reduced by CoCl2 at the concentrations from 500 to 3 000 ?mol?L-1,and the higher CoCl2 doses,the lower cell viability was.CoCl2 induced oxidative stress reaction(increasing ROS production and decreasing MMP).CoCl2 induced inflammatory reaction,enhancing the release of IL-6 and IL-8.CoCl2 at concentrations from 1 000 to 3 000 ?mol?L-1 upregulated HO-1 expression in HaCat cells.Conclusion CoCl2 induces not only oxidative stress,but also inflammatory reaction,increasing the release of both IL-6 and IL-8,as well as HO-1 expression.