Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.

Treatment of angiokeratoma of Mibelli alone or in combination with pulsed dye laser and long-pulsed Nd: YAG laser.

Treatment of angiokeratoma of Mibelli is usually challenging because of the location, the pathogenetic condition and the cosmetic requirements. We present our characteristic treatment with the application of pulsed dye laser PDL and lpNd:YAG laser. All of these lesions were treated by topical anesthesia with Emla. Combined dual PDL-lpNd:YAG (PDL: 595 nm, 5 mm/7 mm, 0.5 ms, 8-10 J/cm(2) ; lpNd:YAG: 3 mm/5 mm, 15 ms, 90-120 J/cm(2) ) treatment was used to treat lesions which with moderate to severe hyperkeratosis and hyperplasia. To the maculopapule ones, the energy density of lpNd:YAG might upgrade to 150 J/cm(2) . Singular PDL (595 nm, 5 mm/7 mm, 0.5 ms, 9-12 J/cm(2) ) treatment was used to treat lesions which with slight hyperkeratosis and hyperplasia. Continuous airflow cooling was always applied during the laser treatment. The treatment interval was 6-12 weeks. Of the 5 patients, 3 of them were cured and 2 of them were improved. All of them were satisfied with the cosmetic results. We recommended the combined dual PDL-lpNd:YAG laser in treating severe hyperkeratotic and hyperplastic angiokeratoma of Mibelli. It can aid in achieving a desirable outcome whilst also reducing the required treatment sessions. However, most patients felt painful during the operation and experienced a severe long term recovery time after operation.

Nuclear ß-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer.

BACKGROUND: Although the prognostic roles of ß-catenin expression in non-small cell lung cancer (NSCLC) have been reported in several immunohistochemical (IHC) studies, the results were not consistent because some studies lack sufficient number of the positive cases or did not evaluate the subcellular localization features of the protein. METHOD: In this study, we have evaluated the expression levels and subcellular localization of ß-catenin and Nanog proteins IHC staining in tissue specimens from 309 patients with NSCLC, and explored their association with clinicopathological features and patient outcome. RESULTS: We showed that patients with negative expression of membranous beta-catenin had a trend towards shorter survival (p=0.064) than those with positive expression. In contrast to previous studies, we found that increased expression of either cytoplasmic or nuclear ß-catenin was strongly associated with poor prognosis and was an independent prognosticator for overall survival (p <0.01). We further found that NSCLC cells frequently exhibited an abundance of nuclear Nanog protein which was significantly correlated with nuclear ß-catenin expression (p <0.01) and poor prognosis (p <0.01). Interestingly, immunofluorescent staining results revealed that increased expression of Nanog and nuclear translocation of ß-catenin occurred concomitantly in response to epidermal growth factor receptor(EGFR) signaling in A549 and H23 cells. Furthermore, western blot analysis show that nuclear ß-catenin rather than cytoplasmic ß-catenin expression in the A549 and H23 cells can be enhanced by adding EGF, Nanog expression in the A549 and H23 cells with knockdown of ß-catenin can not be obviously enhanced by adding EGF. CONCLUSION: We propose that evaluation of subcellular localization of ß-catenin and Nanog expression is of clinical significance for patients with NSCLC.

Synergistic effects of terbinafine and itraconazole on clinical isolates of Fonsecaea monophora.

Our objective was to develop new approaches to the chemotherapy of invasive infections caused by Fonsecaea monophora. The in vitro effects of a combination of terbinafine with itraconazole on 18 clinical isolates were evaluated using a checkerboard microdilution method. The mode of interaction between the two drugs on the 18 isolates was analyzed using fractional inhibitory concentration index (FICI) analysis. FICI analysis demonstrated that 12 (67%) were synergistic, 4 (22%) were additive, and 2 (11%) were indifferent, with no antagonism being observed. The minimal inhibitory concentrations (MICs) obtained with the terbinafine-itraconazole combination were within levels that can be achieved in plasma at clinically relevant doses. Our results indicate the terbinafine-itraconazole combination may be an effective therapy for Fonsecaea monophora infection, which should be tested in clinical setting with patients with this disease.

[Occurrence of Tramadol and Fentanyl Use in Domestic Wastewater in Beijing].

Tramadol (TRA) and fentanyl (FEN) are used as common painkillers in clinical practice, but they have been increasingly abused in recent years due to their addictive nature. Two substances and their metabolites enter wastewater through urine and are collected and treated by wastewater treatment plants (WWTPs) before being discharged into the aquatic environment. In this study, wastewater analysis was performed to examine the patterns of TRA and FEN use in the urban area of Beijing for the first time. Influent and effluent samples were collected from 23 WWTPs during two sampling campaigns. Concentrations TRA in influents were found to range from(10.2±8.7)to(175.3±59.7) ng·L-1, while FEN was not detected in most of the samples, or occurred at very low concentrations. Relatively low TRA removal was observed at plants with activated sludge processes. Moreover, TRA loads in the central area of Beijing were significantly higher than those in the suburban areas. Annual TRA use was estimated through wastewater-based epidemiology. The greatest TRA use, approximately 202.5 kg, was found in Haidian district. Seasonal variation in TRA loads was significant, with greater use in the summer than in winter. The method presented in this study can be used as an important reference for monitoring TRA and FEN use via wastewater-based epidemiology and for assessing the risk of the abuse of these compounds in China.

MicroRNA-21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway.

AIMS: Our study aims to investigate the effect of microRNA-21 (miR-21) on the proliferation, senescence, and apoptosis of glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway. METHODS: Glioma tissues and brain tissues were collected for this study after surgical decompression for traumatic brain injury. RT-qPCR was employed to measure mRNA levels of miR-21, SPRY1, PTEN, PI3K, and AKT, and Western blotting was conducted to determine protein levels of SPRY1, PTEN, PI3K, AKT, p-AKT, Caspase-3, Caspase-9, P53, GSK3, and p-GSK3. Human glioma U87 cells were assigned into the blank, negative control (NC), miR-21 mimics, miR-21 inhibitors, siRNA-SPRY1, and miR-21 inhibitors + siRNA-SPRY1 groups, with human HEB cells serving as the normal group. Cell proliferation, cell cycle, and apoptosis were determined by MTT and flow cytometry, respectively. RESULTS: Compared with control group, an increased expression of miR-21, PI3K, AKT, p-AKT, P53, and p-GSK3, and a decreased expression of SPRY1, PTEN, Caspase-3, and Caspase-9 were observed in the glioma group, and no significant differences were found in the expression of GSK3. SPRY1 was verified to be the target gene of miR-21. Compared with the blank and NC groups, levels of PI3K, AKT, p-AKT, P53, and p-GSK3 increased while levels of SPRY1, PTEN, Caspase-3, and Caspase-9 decreased in the miR-21 mimics and siRNA-SPRY1 groups; the miR-21 inhibitors group reversed the tendency; furthermore, the miR-21 inhibitors group showed decreased cell proliferation but promoted apoptosis, which were opposite to the results of the miR-21 mimics and siRNA-SPRY1 groups. CONCLUSION: MicroRNA-21 might promote cell proliferation and inhibit cell senescence and apoptosis of human glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway.

[Optimization and Validation of the Analytical Method to Detect New Psychoactive Substances in Wastewater].

New psychoactive substances (NPS) are emerging continuously, as the crackdown against traditional drugs becomes stricter. Metabolites of NPSs and the unchanged drugs enter wastewater through urine and are collected and treated by wastewater treatment plants before being discharged into the aquatic environment. Based on previous research, solid phase extraction (SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) were used and the detection method of 11 NPSs was optimized. Influences of wastewater pretreatment procedures, including SPE columns; pH values of water samples; and processes of flushing and redissolving on NPS recoveries were compared. It was shown that the best recovery was achieved when Oasis MCX columns were used and the pH value of wastewater samples was adjusted to 2. A flushing process with 2 mL water at pH=2 followed by 2 mL methanol was needed. Redissolution of the residue after evaporation was best achieved with 400 µL of a 20% methanol water solution. It was indicated by retention times, recoveries, matrix effects, limits of detection, limits of quantification, as well as precision that C18-UPLC-MS/MS and the optimized method are efficient and valid. Influent and effluent samples from 11 municipal wastewater treatment plants in Beijing were analyzed using the optimized method for validation. The validated method can be used as an important reference for monitoring NPSs via wastewater-based epidemiology and for assessing the risk of NPS abuse in China.

[Optimization and Validation of the Analytical Method to Detect Common Illicit Drugs in Wastewater].

Illicit drugs have been recognized as a group of emerging pollutants.Based on previous research,procedures to pre-treat wastewater including SPE column,pH of water samples,and processes of washing,acidifying and re-dissolving were compared.It was found that the best recovery was achieved when wastewater was adjusted to pH=2 and Oasis MCX column was used.It was not necessary to flush the loaded column or to acidify the eluate prior to evaporation using nitrogen steam.After evaporation,it is recommended to redissolve the evaporated samples using 200 µL acetonitrile and 100 µL acetonitrile+100 µL 5 mmol·L-1 ammonium acetate in Milli-Q water for HILIC-UPLC-MS/MS and C18-UPLC-MS/MS,respectively.After comparing retention times,limit of detection,limit of quantification,recoveries,and matrix effects of HILIC and C18 methods,C18-UPLC-MS/MS was chosen.Influent and effluent samples from 12 wastewater treatment plants in Beijing were analyzed using the optimized method for validation.The validated methods set a firm foundation to apply the sewage-based epidemiology to monitor illicit drug abuse in China.

Ingrowing Hair: A Case Report.

Cutaneous pili migrans and creeping eruption caused by parasitic diseases may present as a moving linear lesion in skin. The former, caused by a hair shaft or fragment embedded in the superficial skin or middle dermis, is a rare condition characterized by creeping eruption with a black line observed at the advancing end. In exceptionally rare instance, the hair grows inside the skin and burrows in the uppermost dermis, such a condition has been called "ingrown hair."We report a 30-year-old Chinese man, who was accustomed to pull or extrude the beard hairs, with 1-year history of slowly extending black linear eruption on his right chin. Cutaneous examination revealed a 4-cm long black linear lesion beneath the skin associated with edematous erythema around and folliculitis on both ends of the lesion. After treatment with topical mupirocin ointment, the erythema and folliculitis improved and 2 hairs of the beard with hair follicles were pulled out from the skin. Two weeks later, another similar black line about 1 cm in length in the skin presented on the prior lesional area, which was pulled out by a shallow incision of the skin and was also demonstrated as a beard hair with hair follicle.The patient was diagnosed as "ingrowing hair" with multiple recurrences. The lesions recovered after the beard hairs were pulled out. No recurrence occurred in a year of follow-up.We suggest that "ingrowing hair" is better than "ingrown hair" to describe such a condition. Pulling out the involved hair and correcting the bad practice are its optimal management strategies.

[Concentrations of Ketamine and Norketamine in the Water Environment in Beijing].

Concentrations of ketamine (KET) and its metabolite, norketamine (NK) in sewage water and surface water in Beijing were examined by HPLC-MS/MS. Samples were collected from all the thirteen sewage treatment plants in the urban area and four rivers flowing through the city. Average influent concentrations of KET and NK in 2013 summer ranged from

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients.

BACKGROUND: This study investigated the mechanism of drug resistance in non-small cell lung cancer (NSCLC) patients. We specifically studied whether long noncoding RNAs influence drug resistance in NSCLC to discover new therapeutic targets to increase the survival rate of drug-resistant NSCLC patients. METHODS: Tissue samples were collected from NSCLC patients, and total RNA was isolated for assessment of HOTAIR expression and drug resistance status. MTT assays, tumor sphere formation assays, and western blot were performed to cytologically determine the relationship between HOTAIR expression and cisplatin resistance, as well as to elucidate the potential molecular mechanism involved. RESULTS: HOTAIR expression in tissues of drug-resistant NSCLC patients was higher than that of non-drug-resistant patients. HOTAIR expression was elevated in cisplatin-resistant cell strains (A549/CDDP), and reducing HOTAIR expression increased the sensitivity of A549/CDDP cells to cisplatin. In addition, overexpression of HOTAIR in A549 cells increased resistance to cisplatin. Tumor sphere formation assays showed that the volume of spheres formed by cell strains expressing elevated levels of HOTAIR was greater than that of cell strains with low expression. Western blot experiments showed that elevated expression of HOTAIR upregulated tumor stem cell-related biomarkers and HOTAIR expression was directly related to Klf4 expression. CONCLUSIONS: Elevated HOTAIR expression is associated with drug resistance in NSCLC patients and is related to Klf4 upregulation, providing a new therapeutic target for drug-resistant NSCLC patients.

Clinical significance of HOTAIR expression in colon cancer.

AIM: To detect the expression of the long noncoding RNA HOTAIR in colon cancer and analyze its relationship with clinicopathological parameters of colon cancer. METHODS: Total RNA was extracted from 80 colon cancer tissues and matched tumor-adjacent normal colon tissues and reverse transcribed. Quantitative polymerase chain reaction was used to detect the expression of HOTAIR. The relationship between the expression of HOTAIR and clinicopathological parameters of colon cancer was analyzed. RESULTS: The expression of HOTAIR was significantly higher in colon cancer tissues than in matched tumor-adjacent normal colon tissues (P < 0.05). HOTAIR expression was significantly higher in cases with lymph node metastasis than in those without metastasis; in lowly differentiated and undifferentiated cases than in highly and moderately differentiated cases; and in stages III + IV cases than in stages I + II cases (P < 0.05). CONCLUSION: HOTAIR expression is upregulated in colon cancer, suggesting that HOTAIR plays an important role in the tumorigenesis, development and metastasis of colon cancer. HOTAIR may act as an oncogene and represents a new molecular target for the treatment of colon cancer.

Synthesis of Ser-His-Gly.DNA conjugates.

There are strong interactions between the bases of oligonucleotides. Based on Watson-Crick principle, they can form stable secondary and tertiary structure such as hairpin, duplex, triplex, G-quartet, pseudoknot, which can serve as the scaffold of molecules. Peptides contain active groups such as amino, carboxyl, imidazole, hydroxyl. A protected Ser-His-Gly-Threoninol phosphoramidite was synthesized in this work and was incorporated into a triplex-forming oligonucleotide. The results indicate that the oligonucleotide containing Ser-His-Gly-Threoninol in the middle could still form triplex with the target duplex and the dissociation constant was 0.5 micromol/L.

Impacts of different nanoparticles on functional bacterial community in activated sludge.

Rapidly developing industry raises concerns about the environmental impacts of nanoparticles, but the effects of inorganic nanoparticles on functional bacterial community in wastewater treatment remain unclear. The discriminated effects of silver nanoparticles (Ag-NP) and zinc oxide nanoparticles (ZnO-NP) in a simulated sequencing batch reactor (SBR) system were therefore evaluated by the RNA-based terminal restricted fragment length polymorphism (T-RFLP), 16S rcDNA gene clone library and real-time reverse transcription-PCR (RT-PCR) analyses. Although the COD and NH4-N removal efficiencies were not or slightly reduced by the addition of ZnO-NP and Ag-NP, the functional bacterial community changed remarkably. The denitrification related species were inhibited by high dosage of ZnO-NP and Ag-NP, including Diaphorobacter species, Thauera species and those in the Sphaerotilus-Leptothrix group. However, the bacteria related to sludge bulking, heavy metal resistant and biosorption were increased, especially by ZnO-NPs treatment, including those closely related to Haliscomenobacter hydrossis, Zoogloea ramigera and Methyloversatilis universalis. In addition, Ag-NP and ZnO-NP treatments influenced the functional bacterial community differently. Increasing of bulking related bacteria may help to compensate the COD removal efficiency and to maintain functional redundancy, but could lead to operation failure of activated sludge system when expose to ZnO-NPs.

Cancer stem-like cell properties are regulated by EGFR/AKT/ß-catenin signaling and preferentially inhibited by gefitinib in nasopharyngeal carcinoma.

We report that the epidermal growth factor receptor (EGFR) pathway plays a critical role in regulating cancer stem-like cells (CSCs) in nasopharyngeal carcinoma (NPC), one of the most common malignant tumors in Southeast Asia. Effects of EGFR on maintaining CSCs are mainly mediated by AKT signaling, and ß-catenin is responsible for governing CSC properties in response to EGFR/AKT activation. Significantly, CSCs are enriched by cisplatin and decreased by gefitinib in NPC xenograft models. Upon reimplantation in secondary mice, tumor cells derived from cisplatin-treated mice grew rapidly, whereas regrowth of tumor cells from gefitinib-treated mice was severely diminished. We further demonstrate that expression of EGFR correlates with expression of ß-catenin and Nanog in primary tumor specimens from NPC patients. These findings provide mechanistic and preclinical evidence supporting the use of gefitinib alone or in combination with a chemotherapeutic agent in first-line therapy for patients with NPC. In addition, our results suggest that targeting ß-catenin represents a rational clinical modality for patients whose tumors harbor activated EGFR or AKT.

[Triad, a new approach for contaminated site management].

Remediation of a contaminated site is typically a time-consuming and expensive process. The traditional multistage approach of site management is an important contributor of this lengthy and costly process. The emergence of new characterization technologies and past experiences have led to the development of a new site characterization and remediation approach-Triad approach. In this paper, the three key components of the Triad approach, namely, systematic project planning, dynamic work strategy, and real-time measurement, were elucidated. The advantages and applicability of the Triad approach were demonstrated with case studies. Based on the currect practices of site characterization in China, recommendations are made to promote the application of the Triad approach.

Rapid identification and characterization of Penicillium marneffei using multiplex ligation-dependent probe amplification (MLPA) in paraffin-embedded tissue samples.

Penicillium marneffei infection is a deadly disease and early diagnosis leads to prompt and appropriate antifungal therapy. To develop a sensitive method to diagnose P. marneffei infection, a multiplex ligation-dependent probe amplification (MLPA) assay was adapted. This method can rapidly and specifically detect P. marneffei DNA in cultured cells and paraffin-embedded tissue samples. Three pairs of probes were designed for amplifying the internally (intergenic) transcribed spacer (ITS) region of P. marneffei rRNA using a systematic phylogenetic analysis. These three probe sets produced three amplicons of 198, 166, and 152 bp, respectively, specific for P. marneffei. In contrast, there was only one 198 bp amplicon produced for Talaromyces stipitatus, and one 152 bp amplicon for P. funiculosum, T. intermedius and T. derxii. The probes did not amplify any other reference strains. An array of 40 P. marneffei strains isolated from human patients, bamboo rat, and the local environment was tested by using MLPA, and all were positively identified. Most importantly, P. marneffei in paraffin-embedded tissue specimens from infected human patients was positively amplified by MLPA. The sensitivity and specificity of the MLPA assay could be a useful tool for prompt diagnosis, pathogen characterization, and epidemiological studies of fungal infections.