A person-to-person transmission cluster of severe fever with thrombocytopenia syndrome characterized by mixed viral infections with familial and nosocomial clustering.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with sporadic occurrence and high mortality. Herein, we report an example of the in-hospital transmission of SFTS virus (SFTSV) infections with familial and nosocomial clustering in Zhejiang Province, eastern China, from March to April 2023. The epidemiological investigation and genomic analysis revealed that at least eight suspected cases of SFTS occurred in this cluster, including one death and one asymptomatic case. Our report reemphasizes the risk of familial and nosocomial SFTSV infections in healthcare settings and the urgent need for the long-term systematic surveillance of SFTSV evolution in humans and animals in the eastern coastal regions of China.

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.

Substantial changes of chemical composition and sources of fine particles during the period of COVID-19 pandemic in Taiyuan, Northern China.

To better understand the effects of COVID-19 on air quality in Taiyuan, hourly in situ measurements of PM2.5(particulate matter with an aerodynamic diameter less than 2.5 mm) and chemical components (water-soluble ions, organic carbon (OC), elemental carbon (EC), and trace elements) were conducted before (P1: 1 January-23 January 2020) and during (P2: 24 January-15 February 2020) the coronavirus disease 2019 (COVID-19) outbreak. The average concentrations of PM2.5 dropped from 122.0 µg/m3 during P1 to 83.3 µg/m3 during P2. Compared with P1, except for fireworks burning-related chemical components (K+, Mg2+, K, Cu, Ba), the concentrations of other chemical components of PM2.5 decreased by14.9-69.8%. Although the large decrease of some emission sources, fireworks burning still resulted in the occurrence of pollution events during P2. The analysis results of positive matrix factorization model suggested that six PM2.5 sources changed significantly before and during the outbreak of the epidemic. The contributions of vehicle emission, industrial process, and dust to PM2.5 decreased from 23.1%, 3.5%, and 4.0% during P1 to 7.7%, 3.4%, and 2.3% during P2, respectively, whereas the contributions of secondary inorganic aerosol, fireworks burning, and coal combustion to PM2.5 increased from 62.0%, 1.8%, and 5.5% to 71.5%, 9.0%, and 6.2%, respectively. The source apportionment results were also affected by air mass transport. The largest reductions of vehicle emission, industrial process, and dust source were distinctly seen for the air masses from northwest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11869-021-01082-y.

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.

Prevalence of Antibiotic-Resistant Escherichia coli in Drinking Water Sources in Hangzhou City.

This study investigated the distribution of antibiotic resistant Escherichia coli (E. coli) and examined the possible relationship between water quality parameters and antibiotic resistance from two different drinking water sources (the Qiantang River and the Dongtiao Stream) in Hangzhou city of China. E. coli isolates were tested for their susceptibility to 18 antibiotics. Most of the isolates were resistant to tetracycline (TE), followed by ampicillin (AM), piperacillin (PIP), trimethoprim/sulfamethoxazole (SXT), and chloramphenicol (C). The antibiotic resistance rate of E. coli isolates from two water sources was similar; For E. coli isolates from the Qiantang River, their antibiotic resistance rates decreased from up- to downstream. Seasonally, the dry and wet season had little impact on antibiotic resistance. Spearman's rank correlation revealed significant correlation between resistance to TE and phenicols or ciprofloxacin (CIP), as well as quinolones (ciprofloxacin and levofloxacin) and cephalosporins or gentamicin (GM). Pearson's chi-square tests found certain water parameters such as nutrient concentration were strongly associated with resistance to some of the antibiotics. In addition, tet genes were detected from all 82 TE-resistant E. coli isolates, and most of the isolates (81.87%) contained multiple tet genes, which displayed 14 different combinations. Collectively, this study provided baseline data on antibiotic resistance of drinking water sources in Hangzhou city, which indicates drinking water sources could be the reservoir of antibiotic resistance, potentially presenting a public health risk.

High Prevalence of Plasmid-Mediated Quinolone Resistance and IncQ Plasmids Carrying qnrS2 Gene in Bacteria from Rivers near Hospitals and Aquaculture in China.

Effluents from hospital and aquaculture are considered important sources of quinolone resistance. However, little information is available on the impact of this effluent on nearby rivers. In this study, 188 ciprofloxacin-resistant bacterial isolates obtained from rivers near hospitals and aquaculture were screened for plasmid-mediated quinolone resistance (PMQR) genes. Species identification, antibiotic susceptibility testing, and PMQR gene transferability assessment were conducted for PMQR-positive bacteria. Representative qnrS2-encoding plasmids were subsequently sequenced using a primer-walking approach. In total, 44 isolates (23.4%) were positive for qnr genes (16 qnrB2, 3 qnrS1, and 25 qnrS2) and 32 isolates (17.0%) were positive for aac(6')-Ib-cr. Other PMQR genes were not detected. The qnrB2 and aac(6')-Ib-cr genes had a higher prevalence in aquaculture samples than in hospital samples, and were significantly associated with Enterobacteriaceae (p < 0.05). In contrast, the prevalence of qnrS2 was not site-related, but was significantly associated with Aeromonas spp. (p < 0.05). All PMQR isolates were resistant to three or more classes of antibiotics. Eleven qnrS2-harboring plasmids from Aeromonas spp., including a novel conjugative plasmid pHP18, were selected for sequencing. These plasmids were small in size (6,388-16,197 bp) and belonged to the IncQ or IncU plasmid family, with qnrS2 being part of a mobile insertion cassette. Taken together, our findings suggest that aquaculture is a possible source for aac(6')-Ib-cr and qnrB2 dissemination, and demonstrate the ubiquity of qnrS2 in aquatic environments. Finally, Aeromonas spp. served as vectors for qnrS2 with the help of IncQ-type plasmids.

[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.

[Molecular epidemiology of human metapneumovirus in children with respiratory tract infection in Hangzhou].

OBJECTIVE: To understand the molecular epidemiologic features of human metapnenmovirus (hMPV) in children with respiratory tract infection in Hangzhou. METHODS: 2 593 throat swabs were collected from patients with respiratory tract infections who visited the hospitals with sentinel surveillance programs from January 2011 to December 2013, including 1 676 outpatients and 917 inpatients. Total nucleic acid was extracted from the specimens and the fusion (F) protein gene of hMPV was amplified by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), with positive samples picked to compare with the sequence of hMPV in GenBank, after the sequence of amplification products were determined. Other two types of common respiratory virus were tested using RT-PCR. RESULTS: The overall positive rate in this study was 6.51% (169/2 593), with 6.62% (111/1 676) in outpatients and 6.32% (58/917) in inpatients, but no statistically significant difference was found (χ(2) = 0.086, P = 0.769). The rates was 7.01% in males and 5.72% in females, with no statistically significant difference in different sex (χ(2) = 1.676, P = 0.195). The positive rate was 14.14% (28/198)in the 2-year-olds, 14.01% (22/158)in 3-year olds. The rate in 2-year olds was higher than in other groups, with statistically significant differences between the groups (χ(2) = 38.654, P = 0.000). Of the 169 positive cases, 153 (90.53%) in the younger than 5 years olds. The rates of infection with hMPV in winter and spring were statistically higher than in summer and autumn (χ(2) = 67.032, P = 0.000). The rate of co-infection was 19.52% (33/169). 88 amplified productions were selected for gene sequence analysis, and the F gene homology were 81.6%-100.0% with reference strains in GenBank. Data showed that all the 4 viral subtypes: A2 (52.27% , 46/88), B1 (37.51%, 33/88), B2 (9.09%, 8/88) and A1 (1.13%, 1/88) co-circulated during the study. However, different subtypes appeared predominant in different years:hMPV subtype B1 was in 2011 and 2012, subtype A2 in the end of 2012 and in 2013. Of the 88 specimens, gene sequences were determinate, with A genotype accounted for 67.56% (25/37), B genotype for 32.43% (12/37)in children younger than 1-year olds, and A genotype accounted for 43.13% (22/51), B genotype for 56.86% (29/51)in children above 1-year olds. Significant differences between the two groups (χ(2) = 5.143, P = 0.023) were noticed. CONCLUSION: It was confirmed that hMPV was one of the substantial pathogens causing the respiratory tract infections. Data from our study suggested that the peak time of hMPV infection predominated during winter and spring in Hangzhou. Both hMPV subtype B1 and subtype A2 were found popular in this study, with hMPV genotype A dominating in children younger than 1-year olds.

[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.

Identification and analysis of the gene cluster involved in biosynthesis of paenibactin, a catecholate siderophore produced by Paenibacillus elgii B69.

Bacteria belonging to the genus Paenibacillus are recognized as rich sources of bioactive natural products. To date, there are few characterized siderophores from this genus. Here, through genome analysis, we identified a non-ribosomal peptide biosynthetic gene cluster (pae) responsible for siderophore assembly in Paenibacillus elgii B69. The 12.8 kb gene cluster comprises six open reading frames encoding proteins similar to the components of the bacillibactin biosynthetic machinery and bacillibactin esterase. To examine the product of the pae gene cluster, we cultured P. elgii B69 in iron-deficient medium for siderophore expression. A novel siderophore structurally similar to bacillibactin, designated paenibactin, was purified and characterized. Its structure was determined as a cyclic trimeric lactone of 2,3-dihydroxybenzoyl-alanine-threonine. The involvement of the pae gene cluster in paenibactin biosynthesis was confirmed by the biochemical assay of adenylation domain specificity. Furthermore, we demonstrated that the pae gene cluster evolves from an ancestral bacillibactin biosynthetic gene cluster via sequence and phylogenetic analyses. The structural difference between paenibactin and bacillibactin may stem from a mutation-induced change in the adenylation domain specificity. Based on these findings and published models for bacillibactin, we proposed models for paenibactin biosynthesis, ferric-paenibactin uptake and paenibactin-bounded iron release.

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.

Paenibacillus tianmuensis sp. nov., isolated from soil.

Two closely related, Gram-stain-negative, rod-shaped, spore-forming strains, B27(T) and F6-B70, were isolated from soil samples of Tianmu Mountain National Natural Reserve in Zhejiang, China. Phylogenetic analysis based on 16S rRNA gene and rpoB sequences indicated that the isolates were members of the genus Paenibacillus. Both isolates were closely related to Paenibacillus ehimensis IFO 15659(T), Paenibacillus elgii SD17(T) and Paenibacillus koreensis YC300(T) (≥ 95.2 % 16S rRNA gene sequence similarity). DNA-DNA relatedness between strain B27(T) and P. ehimensis DSM 11029(T), P. elgii NBRC 100335(T) and P. koreensis KCTC 2393(T) was 21.2, 28.6 and 16.8 %, respectively. The major cellular fatty acids of strains B27(T) and F6-B70 were anteiso-C(15 : 0) and iso-C(15 : 0). The cell wall contained meso-diaminopimelic acid. The two isolates differed from their closest neighbours in terms of phenotypic characteristics and cellular fatty acid profiles (such as variable for oxidase, negative for methyl red test, unable to produce acid from d-fructose and glycogen and relatively higher amounts of iso-C(15 : 0) and lower amounts of C(16 : 0) and iso-C(16 : 0)). Strains B27(T) and F6-B70 represent a novel species of the genus Paenibacillus, for which the name Paenibacillus tianmuensis sp. nov. is proposed. The type strain is B27(T) ( = DSM 22342(T)  = CGMCC 1.8946(T)).

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)).

Taxonomic study of a chromomycin-producing strain and reclassification of Streptomyces cavourensis subsp. washingtonensis as a later synonym of Streptomyces griseus.

A chromomycin-producing actinomycete, strain AP19, was isolated from a sample of faeces collected from Foping national nature reserve in China. Chemotaxonomic and morphological properties indicated that the novel isolate was a member of the genus Streptomyces. Phylogenetic analyses based on an almost complete 16S rRNA gene sequence of the strain and on the 120-nt nucleotide variable gamma-region of this molecule revealed that it was closely related to Streptomyces griseus ISP 5236(T) and Streptomyces cavourensis subsp. washingtonensis ATCC 27732(T). DNA-DNA relatedness values among these strains were above 70 %. Streptomyces cavourensis subsp. washingtonensis could be readily distinguished from Streptomyces cavourensis ATCC 14889(T) by differing BOX-PCR fingerprinting patterns, relatively low 16S rRNA gene sequence similarity and a low DNA-DNA relatedness value. It is proposed, therefore, that Streptomyces cavourensis subsp. washingtonensis is a later synonym of Streptomyces griseus.

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.