Voriconazole-induced severe skin allergy and neurological adverse event in a liver failure patient: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. CASE SUMMARY: A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration.

[Comprehensive mass spectrum analysis of two flavone-6,8-C-di-glycosides and its application by high resolution electrospray ionization tandem mass spectroscopy in both negative and positive ion modes].

The tandem mass spectrum of apigenin-6,8-C-di-glucoside( 1) and apigenin-6-C-glucose-8-C-rhamnoside( 2) were obtained by high resolution electrospray ionization mass spectrometry( HR-ESI-MS/MS) in both positive and negative ion modes. The elemental composition of each ion was determined according to its accurate mass-to-charge,hence,the fragmentation pathways of each compound were proposed in both negative and positive ion modes. Comprehensive analysis of each ion and its proposed fragmentation pathways of the two compounds was initially conducted in both negative and positive ion mode HR-ESI-MS/MS to explore the diagnostic ions for flavone-6,8-C-di-glycosides and the characteristic ions for each compound and their cleavage rules. The results showed that a family of fragmentation ions with m/z 353,325,311,297 in ESI(-)-MS and m/z 355,325,307,295 in ESI( +)-MS could be the diagnostic ions of flavone-6,8-C-di-glycoside,and characteristic neutral loss could be assigned to glycosyl substitution,for example,neutral losses of C_4H_8O_4( 120),C_3H_6O_3( 90),C_2H_4O_2( 60) for glucoside substitution while neutral losses of C_4H_8O_3(104),C_3H_6O_2( 74),C_2H_4O( 44) for rhamnoside substitution. Furthermore,only one H_2O loss from mother ion( [M-H]-) was observed for 1 & 2 in ESI(-)-MS while five to six H2 O loss from mother ion( [M+H]+) was observed for 1 & 2 in ESI( +)-MS to produce a family of ions by subsequent loss of H_2O,which could be applied for glucosyl difference. The flavone-6,8-C-di-glycosides in both ESI( +)-MS and ESI(-)-MS showed the cleavage similarity at sugar substitutions. However,there were much more differences by the fragmentation pathways and neutral losses between ESI( +)-MS and ESI(-)-MS as following,hyperconjugation ions by subsequent loss of H_2O from precursor ions of flavone-6,8-C-di-glycosides in ESI( +)-MS were not observed in ESI(-)-MS; the subsequent neutral loss of CH_2O in ESI( +)-MS were rarely observed in ESI(-)-MS; the loss of CO only happen at C-ring of flavone ESI( +)-MS other than glycosyl position in ESI(-)-MS; the C4-chain neutral loss of flavone-6,8-C-di-glycosides happened at 8-C-glycosyl position other than at 6-C-glycosyl position. The above cleavage rules and diagnostic ions of ESI( +)-MS were successfully applied for the structure identification of 4 flavone-6 C,8 C-diglycosides from the stem extract of Dendrobium officinale as vicenin Ⅱ,vicenin Ⅰ,isoschaftoside,schaftoside as well as one flavone-O-glysoside named rutin,which were supported by ESI(-)-MS data as well.

LncRNA SNHG1 alleviates myocardial ischaemia-reperfusion injury by regulating the miR-137-3p/KLF4/TRPV1 axis.

AIMS: Myocardial ischaemia-reperfusion injury (MIRI) contributes to serious myocardial injury and even death. Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in the occurrence and development of MIRI. Here, the detailed molecular mechanism of lncRNA SNHG1 in MIRI was explored. METHODS AND RESULTS: A cell model of MIRI was established through hypoxia/reoxygenation (H/R) stimulation. Cell viability and pyroptosis were evaluated utilizing MTT, PI staining, and flow cytometry. Interleukin (IL)-1ß and IL-18 secretion levels were examined by ELISA. The gene and protein expression were detected by RT-qPCR and western blot, respectively. Dual luciferase reporter gene, RIP and ChIP assays were performed to analyse the molecular interactions. The results showed that lncRNA SNHG1 overexpression alleviated H/R-induced HL-1 cell pyroptosis (all P < 0.05). LncRNA SNHG1 promoted KLF4 expression by sponging miR-137-3p. miR-137-3p silencing alleviated H/R-induced pyroptosis in HL-1 cells (all P < 0.05), which was abolished by KLF4 knockdown (all P < 0.05). KLF4 activated the AKT pathway by transcriptionally activating TRPV1 in HL-1 cells (all P < 0.05). TRPV1 knockdown reversed the alleviation of SNHG1 upregulation on H/R-induced pyroptosis in HL-1 cells (all P < 0.05). CONCLUSIONS: These results showed that lncRNA SNHG1 assuaged cardiomyocyte pyroptosis during MIRI progression by regulating the KLF4/TRPV1/AKT axis through sponging miR-137-3p. Our findings may provide novel therapeutic targets for MIRI.

Utilization and expenses of outpatient services among tuberculosis patients in three Chinese counties: an observational comparison study.

BACKGROUND: The China-Gates TB project Phase II implemented case-based payment reform in three Chinese counties in 2014, designed specifically for patients diagnosed with Tuberculosis (TB). This study aimed to examine the changes in utilization and expenses of outpatient services before and after the reform implementation, among TB patients in the three counties in China. METHODS: We collected quantitative data using surveys in 2013 (baseline year) and 2015 (final year). We used outpatient hospital records to measure service utilization and medical expenses of TB patients. We conducted qualitative interviews with local health authorities, officers of health insurance agencies, and hospital managers (n = 18). We utilized three focus group discussions with hospital staff and TB doctors and nurses. The χ2 tests and Mann-Whitney U tests were used to analyse quantitative data, and the thematic analysis using a framework approach was applied to analyse qualitative data. RESULTS: Dantu and Yangzhong counties enacted TB-specific case-based payment method in 2014. Jurong County maintained global budget payment but raised the reimbursement rate for TB care. Compared to the baseline, the percentage of TB patients in Dantu and Yangzhong with eight or above outpatient visits increased from 7.5 to 55.1% and from 22.1 to 53.1% in the final survey, respectively. Jurong experienced the opposite trend, decreasing from 63.0 to 9.8%. In the final survey, the total outpatient expenses per patient during a full treatment course in Dantu (RMB 2939.7) and Yangzhong (RMB 2520.6) were significantly higher than those in the baseline (RMB 690.4 and RMB 1001.5, respectively), while the total outpatient expenses in Jurong decreased significantly (RMB 1976.0 in the baseline and RMB 660.8 in the final survey). Health insurance agencies in Dantu and Yangzhong did not approve the original design with outpatient and inpatient expenses packaged together, revealed by qualitative interviews. Furthermore, staff at designated hospitals misunderstood that health insurance agencies would only reimburse actual expenses. Many TB doctors complained about their reduced salary, which might be due to decreased hospital revenue generated from TB care after the payment method reform. CONCLUSIONS: The intended effect on cost containment of case-based payment was not evident in Dantu and Yangzhong. In Jurong, where the global budget payment system maintained with the reimbursement rate enhanced, we found an effect on cost containment, but the quality of TB care might be compromised. The TB-specific case-based payment method could be redesigned to combine payment on outpatient and inpatient expenses and to set an appropriate payment standard for TB care during a full treatment course. Local health insurance agencies have to provide explicit explanations on the payment method. TB care providers should be provided with proper incentives. Monitoring and evluaiton on the quality of TB care should be undertaken at regular intervals.