Simultaneous development of pneumonitis and autoimmune diabetes secondary to immune checkpoint inhibitor treatment with durvalumab in an advanced small cell lung cancer patient: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed. PATIENT CONCERNS: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab. DIAGNOSES: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus. INTERVENTIONS: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed. OUTCOMES: After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy. LESSONS: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.

5-Aza-2-deoxycytidine alleviates the progression of primary biliary cholangitis by suppressing the FoxP3 methylation and promoting the Treg/Th17 balance.

Primary biliary cholangitis (PBC) is a common autoimmune liver disease manifested by the infiltration of CD4+ T cells, and the subsequent targeted injury of biliary epithelial cells (BECs). As important components of CD4 subsets, the Treg/Th17 axis maintains an immunological balance between self-tolerance and inflammation in the liver microenvironment. However, the role and regulatory mechanism of the Treg/Th17 axis in PBC remain unclear. In this study, we examined the Treg/Th17 axis in PBC patients and found that the Treg/Th17 axis was imbalanced in PBC at both the transcriptional and cellular levels, with Treg being a weak candidate, which correlates with the PBC progression. This imbalanced Treg/Th17 axis was likely to be affected by the FoxP3 hypermethylation, which was related to the increase of DNA methyltransferase. Furthermore, the effect of 5-Aza-2-deoxycytidine (DAC)-mediated FoxP3 demethylation on PBC mice was investigated. We verified that DAC significantly suppressed the FoxP3 methylation and rebuilt the Treg/Th17 balance, resulting in the alleviation of liver lesions and inflammation. Taken together, our data indicate that DAC plays a positive role in alleviating the progression of PBC through the inhibition of DNA methylation of FoxP3 to rebuild the balanced Treg/Th17 axis. DAC could be considered as a potential candidate for the development of new anti-inflammation strategies in the treatment of PBC.

Consensus in Identification and Stability of Symptom Clusters Using Different Symptom Dimensions in Newly Diagnosed Acute Myeloid Leukemia Patients Undergoing Induction Therapy.

CONTEXT: An unresolved issue in symptom cluster (SC) research is that the numbers and types of SCs vary based on the multiple dimensions of the experienced symptoms that are used for SC identification. OBJECTIVE: This study aimed to identify SCs using the ratings of occurrence, severity, and distress in newly diagnosed acute myeloid leukemia (AML) patients at three stages of their induction therapy (i.e., T1, T2, and T3). Then, we evaluated the consensus among the numbers and types of symptoms in each SC identified by multiple dimensions over time. METHOD: The Chinese version of the Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress ratings of 32 symptoms in patients newly diagnosed with AML during their induction therapy. Exploratory factor analysis was used for SCs identification. RESULTS: Using the three dimensions in the AML patients (n = 126), four SCs were identified at T1 and T3 and three SCs were identified at T2. The number of symptoms in individual SCs varied over time, whereas the specific symptoms in SCs remained similar over time. The severity ratings fit the data better than did the ratings of occurrence and distress. CONCLUSION: These findings provided insights into the most common SCs in AML patients undergoing induction therapy by multidimensional evaluation and could lay the foundation for future targeted symptom interventions. Further studies are needed to explore the mechanisms of SCs in AML patients undergoing the chemotherapy.

[Pollution characteristics of organic and elemental carbon in PM2.5 in Taiyuan].

PM2.5 samples were collected at four sampling sites to study pollution characteristics of carbonaceous aerosols in Taiyuan during winter and summer. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were analyzed by carbon analyzer, and the characteristics including pollution levels, temporal and spatial distributions of OC and EC, secondary organic carbon (SOC) and relationships of OC and EC were discussed in detail. The average concentrations of OC and EC in winter were 22.3 µg x m(-3) and 18.3 µg x m(-3), respectively, while in summer were 13.1 µg x m(-3) and 9.8 µg x m(-3), respectively. The concentrations of total carbon aerosol (TCA) accounted for 56.6% of PM2.5 in winter, and 36.5% in summer; the concentrations of OC and EC at four sites in winter were higher than those in summer, OC and EC levels showed a good uniformity in winter while in summer, the spatial distributions of OC and EC were obviously different; SOC levels were lighter than other cities; the correlation between OC and EC was stronger in winter than that in summer.

[Characteristic of elements in PM2.5 and health risk assessment of heavy metals during heating season in Taiyuan].

The fine particulate matter (PM2.5) sampled during heating season in Taiyuan city and nineteen samples were used to investigate elemental concentrations and its source potential ecological risks of heavy metals, and to assess human exposure and health risk. The result indicated that main elements were Si, Ca, Al, Na, Mg, K, Fe in PM2.5. The main sources of elements in PM2.5 were divided into five categories including soil dust (43.46%), coal burning (15.69%), vehicle emission (13.41%), industrial dust (9.89%) and the construction cement dust (9.03%). Moreover, the order of potential ecological risk index of heavy metals in PM2.5 was Cd > Ni > Hg > Pb > Cu > Zn > As > Co > Cr > Mn, and the ecological hazards were high. The main exposure of heavy metals in atmosphere was respiratory inhalation . The exposure quantity for children was significantly higher than that for adult. The hazard index values suggested a potential non-carcinogenic risk in PM2.5.

[Analysis of infection status and pathogenic features of human metapneumovirus among children in Hangzhou between year 2009 and 2011].

OBJECTIVE: To study the infection status and pathogenic features of human metapneumovirus (hMPV) among children with acute respiratory tract infection in Hangzhou. METHODS: A total of 372 children less than 14 years old with acute respiratory tract infections were recruited as subjects from the pediatric clinic or intensive care unit (ICU) of 3 hospitals in Hangzhou during November 2009 to January 2010, and November 2010 to January 2011. A total of 372 specimens were collected, including 351 respiratory swab, 9 nasopharyngeal aspirate material, 8 endotracheal aspirate material and 4 sputum. The total nucleic acid was then extracted from the specimens, and the nucleoprotein (N) gene of hMPV was amplified by RT-PCR, whose positive products were sequenced and analyzed. Africa green monkey kidney cells (Vero-E6) were applied to culture hMPV among the positive samples; meanwhile fluorescence quantitative RT-PCR was adopted to test other respiratory virus infection. RESULTS: Out of 372 patients, 42 (11.2%) were positive for N gene of hMPV. The positive rate of hMPV among boys was 11.5% (26/226), and correspondingly 10.9% (16/146) among girls. The difference showed no statistical significance (χ(2) = 0.026, P > 0.05). The youngest patient was only 2 month-old and the eldest patient was 14 years old. The median of the patients' age was 24 months. Fifteen positive samples amplified by RT-PCR were sequenced, and all turned out to be subtype B1; whose similarity to GD165 found in Guangdong was 98.1% - 99.5% and similarity to BJ1897 in Beijing was 87.8% - 89.2%. The co-infection rate between hMPV and other respiratory virus was 45.2% (19/42); most of which was between hMPV and respiratory syncytial virus, whose rate at 26.1% (11/42). CONCLUSION: hMPV was the single genotype relevant with the acute respiratory tract infection disease among children in Hangzhou district; however, the co-infection with other respiratory virus did exist.

Paenimacrolidin, a novel macrolide antibiotic from Paenibacillus sp. F6-B70 active against methicillin-resistant Staphylococcus aureus.

Paenibacillus sp. F6-B70 was selected from several dozens of isolates with activity against methicillin-resistant Staphylococcus aureus using a 16S rDNA-based screening method. F6-B70 contained polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) clusters in its genome revealed by PCR amplification of conserved adenylation and ketosynthase (KS) domains. Phylogenetic data suggested that the strain hosts trans-AT PKSs and their product may be a branched molecule. An antibiotic was subsequently isolated from the methanol extract of F6-B70 cells. The molecular formula of the antibiotic was deduced to be C(33) H(50) NaO(6) ([M + Na](+) , m/z 565.3505) by analysis of electrospray ionization mass spectral data. Elucidation of the structure by nuclear magnetic resonance and infrared spectroscopy revealed that the active compound, paenimacrolidin (PAM), was a novel 22-membered macrolide with side-chains. The new antibiotic, mainly as a bacteriostatic agent, inhibits a couple of multidrug-resistant Staphylococcus sp. strains. The antibiotic capacity of PAM was compromised by its instability, which can be overcome significantly with addition of an anti-oxidant. To our knowledge, this is the first report of the isolation of an active macrolide from paenibacilli, which may be a promising source of novel antibiotics.

Bacillus tianmuensis sp. nov., isolated from soil in Tianmu Mountain national natural reserve, Hangzhou, China.

In a project aiming to isolate strains with the ability to produce nonribosomal peptides, a gram-negative, endospore-forming, rod-shaped strain, designated B5(T), was isolated from a soil sample collected from Tianmu Mountain national natural reserve in Hangzhou, China. Strain B5(T) contained meso-diaminopimelic acid in the cell wall peptidoglycan. The major cellular fatty acids were anteiso-C(15:0) and iso-C(15:0). The DNA G+C content was 42.5 mol%. The phylogenetic analysis based on 16S rRNA gene sequence indicated that strain B5(T) fell within the genus Bacillus, with highest sequence similarity values to Bacillus barbaricus DSM 14730(T) (96.4%) and Bacillus macauensis JCM 13285(T) (95.5%). The isolate, however, could be distinguished from Bacillus strains with validly published names by low 16S rRNA gene sequence similarity values, distinct phenotypic and chemotaxonomic characteristics. On the basis of these polyphasic evidences, it is demonstrated that the isolate B5(T) represents a novel species of the genus Bacillus, for which the name Bacillus tianmuensis sp. nov. is proposed. The type strain is B5(T) (=DSM 22111(T)=CGMCC 1.8879(T)).

Isolation and identification of newly isolated antagonistic Streptomyces sp. strain AP19-2 producing chromomycins.

A new antagonistic strain of actinomycete, designated AP19-2, was isolated from the feces of giant pandas inhabiting the Foping National Nature Reserve in China. Cultural characteristic studies strongly suggested that this strain is a member of the genus Streptomyces. The nucleotide sequence of the 16S rRNA gene of strain AP19-2 evidenced profound similarity (97-99%) with other Streptomyces strains. Two pure active molecules were isolated from a fermentation broth of Streptomyces sp. strain AP19-2 via extraction, concentration, silica gel G column chromatography, and HPLC. The chemical structures of the two related compounds (referred to as chromomycin A2 and chromomycin A3) were established on the basis of their Infrared spectra (IR), High Resolution Electrospray Ionization Mass Spectrometry (HR-ESI-MS), and Nuclear Magnetic Resonance (NMR) data, and by comparison with published data.