Bayer AG.

i Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR 34 /L98H mutation, whereas four carry the TR 34 /L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR 34 / L98H isolates, while the TR 34 /L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azolesusceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.

Skin can be infected by many types of microorganisms, most commonly by gram-positive strains of Staphylococcus and Streptococcus spp. Treatment of Staphylococcus aureus (S. aureus) infections, particularly that of methicillin resistant Staphylococcus aureus (MRSA), is a challenge in clinical practice. Ozone therapy has proven to be one of the strongest antiseptics against the majority of microorganisms involved in skin infections. The purpose of the present study was to evaluate the microbicidal effects of topical ozone therapy on S. aureus and MRSA, and determine the clinical efficacy of ozone therapy on patients with MRSA skin infection. Microbicidal effects of ozonated oil and ozonated water were determined by plating and Kirby Bauer methods. Clinical efficacy and safety of topical ozone were evaluated in two cases with skin MRSA infection. The killing rates of ozonated oil for S. aureus and MRSA were greater when compared with the control oil group. Almost 100% of S. aureus were eliminated by ozonated oil following 5 min. Almost 100% MRSA were eliminated by ozonated oil following 15 min. In addition, 100% S. aureus and 100% MRSA were eliminated by ozonated water in 1 min. The inhibition zone diameters of ozonated oil for S. aureus and MRSA were 17 and 13 mm, respectively, which were significantly larger than the control group. Both cases of skin MRSA infection were completely healed with ozone therapy. In conclusion, ozone therapy is a potential treatment for S. aureus and MRSA skin infection as it has great efficacy, few side effects and low-costs.

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Rationale: Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. The first choice for GBM is surgery, and followed by a combination of radiotherapy and chemotherapy. There are limited treatments for patients with recurrent GBM. Relapsed patients usually have a worse prognosis, and with a median survival time of <6 months. Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. This drug has been used to treat advanced lung cancer. Patient concerns: We present a case of recurrent GBM was treated with anlotinib in this report. The patient was diagnosed with GBM in August 2016 and treated with surgery and temozolomide (TMZ) chemotherapy. She was diagnosed with recurrence in February 2017 following which she was treated with gamma knife and TMZ chemotherapy. In November 2017, the patient presented with decreased vision in left eye. She was given radiation and her left eye vision returned to normal after radiation. On May23, 2018, the patient reported a decrease in left visual acuity again. Diagnoses: Brain magnetic resonance imaging (MRI) showed progression of the disease, and the tumor invaded the left optic nerve. Interventions: This patient was administer anlotinib 12 mg po qd (d1–14, 21days as a cycle). Three cycles anlotinib were given to this patient. Outcomes: The patient reported her left visual acuity increased over 10 days after first cycle of anlotinib treatment. MRI scan revealed tumor volume shrinks, especially the part that invades the left optic nerve shrinks significantly at 26 days after anlotinib treatment on August 11, 2018. However, the tumor progressed in 2 months after using of anlotinib. From the beginning of the application of anlotinib to death, her survival time was 110 days. Lessons: Anlotinib treatment with mild side effects may be a new option for the patients with recurrent glioblastoma.

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Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.