Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature.

Background: Nivolumab is the first programmed cell death receptor 1 (PD-1) inhibitor approved in China. Compared with chemotherapy, nivolumab has shown advantages of good efficacy and safety in the treatment of a variety of tumors. However, due to its short time of use in China and lack of safety experience, clinical understanding of its adverse reactions has not been sufficiently elucidated. In recent years, cases of diabetic ketoacidosis caused by nivolumab have been reported in the emergency department, which has aroused our concern. Case Description: Here we present a serious case of diabetic ketoacidosis in a 69-year-old woman with invasive mucinous adenocarcinoma of the lung, which occurred following therapy with the PD-1 inhibitor nivolumab and dendritic cell/cytokine-induced killer cell (DC/CIK) immunotherapy. She presented with diabetic ketoacidosis 5 days after the second cycle of nivolumab administration. The patient presented with dry mouth symptoms, a maximum blood glucose of 511.2 mg/dL, hemoglobin A1c (HbA1c) level of 7.4%, urine ketone body value of 3+, and extracellular fluid residual alkali level of -3.8 mmol/L. Normal saline and insulin was initiated. The patient had no history of obesity or family history of diabetes. She received a single dose of 3.75 mg of dexamethasone treatment during this period of time which resulted in cough improvement, but did not explain the onset of the diabetes. She was treated with insulin, sitagliptin phosphate tablets and acarbose tablets. Diabetic ketoacidosis was considered an immune-related toxicity caused by nivolumab, and consequently, treatment with nivolumab was suspended. Patient was maintained under insulin treatment with a blood glucose levels normalization. Conclusions: The incubation period of nivolumab-induced diabetic ketoacidosis is dispersive and the clinical risk is high. Patients need life-long insulin therapy. Blood glucose and HbA1c should be monitored routinely before and during nivolumab immunotherapy to avoid the occurrence of diabetic ketoacidosis. After the occurrence of diabetic ketoacidosis, insulin should be used to actively control blood glucose and do a good job in medication education to ensure long-term compliance of patients. Nivolumab should only be initiated if the patient has a clinical benefit under stable glucose control.

Tenggerimyces flavus sp. nov., isolated from soil in a karst cave, and emended description of the genus Tenggerimyces.

A novel actinomycete, designated strain S6R2A4-9T, was isolated from a soil sample collected from a karst cave in Henan Province, China, and subjected to a polyphasic taxonomic study. This isolate grew optimally at 25-28 °C, pH 6.5-8.0 and in the absence of NaCl. The substrate mycelium of the isolate was well developed with irregular branches. Aerial mycelium fragmented into long, rod-shaped elements. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain S6R2A4-9T resided in the cluster of the genus Tenggerimyces within the family Nocardioidaceae and shared the highest 16S rRNA gene sequence similarity (98.98 %) with Tenggerimyces mesophilus I12A-02601T. The G+C content of the genomic DNA was 67.0 mol%. The strain contained glucose, ribose and xylose in its whole-cell hydrolysates. Strain S6R2A4-9T possessed a novel variation of peptidoglycan derived from the type A1γ meso-Dpm-direct. The polar lipids consisted of diphosphatidylglycerol, N-acetylglucosamine-containing phospholipid, phosphatidylinositol mannoside, phosphatidylglycerol, phosphoglycolipids and glycolipids. The predominant menaquinones were MK-10(H6) and MK-10(H8). The major fatty acids were C16 : 0, iso-C16 : 0 and 10-methyl C17 : 0. The level of DNA-DNA relatedness between strain S6R2A4-9T and T. mesophilus I12A-02601T was 27.6 ± 3.0 %, which was low enough to indicate that the strain represents a distinct species of the genus Tenggerimyces. On the basis of the polyphasic taxonomic evidence, a novel species, Tenggerimyces flavus sp. nov., is proposed. The type strain of the novel species is S6R2A4-9T ( = DSM 28944T = CGMCC 4.7241T).

[Raman spectroscopic quantitative analysis of cluster structure of binary alkali silicate glasses].

A calibration method for Raman spectroscopic quantitative analysis of binary alkaline silicate glasses is proposed. By applying ab initio quantum chemistry simulation, Raman optical activities (ROA) of various cluster units consisting of silicon-oxygen tetrahedra (SiOT) with different number of non-bridging oxygen (NBO) can be obtained. Thus, experimental results could be calibrated in order to reflect and represent directly the true relative density of various silicon-oxygen tetrahedra existing inside the silicate glasses. Cation effect on the intensity of Raman bands was also observed and discussed.

[Temperature dependent Raman spectra and micro-structure study of cuspidine in solid and liquid phases].

Cuspidine plays an important role in conventional metallurgical continuous casting mould flux. An UV laser source was used to record its ambient and high temperature Raman spectra (temperature range: 298-1 723 K) combined with a charge coupled device (CCD) detector. Both increasing and decreasing processes as well as characteristic spectra and shifts in wavenumber were observed. Micro-structure of cuspidine in liquid state is not unitary and different from that in solid state, suggesting multi clusters coexisting. Density functional theory (DFT) simulation method was applied to calculate its wavenumbers of Raman active vibrations by introducing the crystal spatial configuration model of cuspidine. Thus the experimental vibrational wavenumbers of the characteristic peaks could be assigned. This will help study physical and chemical behavior of cuspidine in continuous casting mould flux and provide an unique in-situ method under varying temperature with Raman spectroscopic technique.