Human inflammatory dendritic cells in malignant pleural effusions induce Th1 cell differentiation.

Dendritic cells are crucial for the initiation and regulation of immune responses against cancer and pathogens. DCs are heterogeneous and highly specialized antigen-presenting cells. Human DCs comprise several subsets with different phenotypes and functional properties. In the steady state, human DC subsets have been well studied. However, the components of DC subsets and their immune functions during the inflamed setting are poorly understood. We identified and characterized DC subsets in the malignant pleural effusions of NSCLC patients. We analyzed the capacity of these DC subsets to induce T-cell differentiation. We observed the presence of inflammatory DCs (infDCs) and macrophages in the malignant pleural effusions of NSCLC patients, as identified by the CD11C+HLA-DR+CD16-BDCA1+ and CD11C+HLA-DR+CD16+BDCA1- phenotypes, respectively. InfDCs represented approximately 1% of the total light-density cells in the pleural effusion and were characterized by the expression of CD206, CD14, CD11b, and CD1α, which were absent on blood DCs. InfDCs also expressed CD80, although at a low level. As infDCs did not express CD40, CD83 and CD275, they remained functionally immature. We found that TLR agonists promoted the maturation of infDCs. Compared with macrophages, infDCs had a weaker capacity to phagocytose necrotic tumor cell lysates. However, only infDCs induced autologous memory CD4+ T-cell differentiation into Th1 cells. For the first time, we found that infDCs were present in the malignant pleural effusions of NSCLC patients. We conclude that infDCs represent a distinct human DC subset and induce Th1 cell differentiation in the presence of TLR agonists.

Color fringe-projected technique for measuring dynamic objects based on bidimensional empirical mode decomposition.

A triple-frequency color fringe-projected technique is presented to measure dynamic objects. Three fringe patterns with a carrier frequency ratio of 1:3:9 are encoded in red, green, and blue channels of a color fringe pattern and projected onto an object's surface. Bidimensional empirical mode decomposition is used for decoupling the cross talk among color channels and for extracting the fundamental frequency components of the three fringe patterns. The unwrapped phase distribution of the high-frequency fringe is retrieved by a three-step phase unwrapping strategy to recover the object's height distribution. Owing to its use of only a single snapshot, the technique is suitable for measuring dynamically changing objects with large discontinuity or spatially isolated surfaces.

Molecular characteristics and risk factor analysis of Staphylococcus aureus colonization put insight into CC1 colonization in three nursing homes in Shanghai.

Research indicates that Staphylococcus aureus colonization in the elderly with predisposing risks is associated with subsequent infection. However, the molecular epidemiology and risk factors for S. aureus colonization among residents and staff in nursing homes (NHs) in China remain unclear. A multicenter study was conducted in three NHs in Shanghai between September 2019 and October 2019. We explored the prevalence, molecular epidemiology, and risk factors for S. aureus colonization. All S. aureus isolates were characterized based on antimicrobial resistance, virulence genes, multilocus sequence typing (MLST), staphylococcus protein A (spa) typing, and staphylococcal cassette chromosome mec (SCCmec) typing. NH records were examined for potential risk factors for S. aureus colonization. S. aureus and methicillin-resistant S. aureus (MRSA) isolates were detected in 109 (100 residents and 9 staff, 19.8%, 109/551) and 28 (24 residents and 4 staff, 5.1%, 28/551) subjects among 496 residents and 55 staff screened, respectively. Compared to methicillin-susceptible S. aureus isolates, all 30 MRSA isolates had higher resistance rates to most antibiotics except minocycline, rifampicin, linezolid, vancomycin, and teicoplanin. Sequence type (ST) 1 (21.3%) was the most common sequence type, and t127 (20.5%) was the most common spa type among 122 S. aureus isolates. SCCmec type I (70%) was the dominant clone among all MRSA isolates. CC1 (26/122, 21.3%) was the predominant complex clone (CC), followed by CC398 (25/122, 20.5%), CC5 (20/122, 16.4%) and CC188 (18/122, 14.8%). Female sex (OR, 1.70; 95% CI, 1.04-2.79; P = 0.036) and invasive devices (OR, 2.19; 95% CI, 1.26-3.81; P = 0.006) were independently associated with S. aureus colonization.

Molecular Epidemiology and Antimicrobial Resistance of Haemophilus influenzae in Adult Patients in Shanghai, China.

Background: The serotype and antimicrobial resistance of Haemophilus influenzae in adult patients have changed due to the application of antimicrobials and H. influenzae type b (Hib) vaccine worldwide. However, the epidemiologic characteristics of H. influenzae in Shanghai are still unavailable. Objective: To determine the serotype distribution, antimicrobial resistance and multilocus sequence type (MLST) of H. influenzae in adult patients in Shanghai. Methods: A total of 51 clinical isolates from adult patients were consecutively collected. Serotypes were determined according to specific capsule gene, bexA, amplified by PCR. Antimicrobial susceptibility test was carried out by the broth microdilution method. ß-lactamase production was detected by cefinase disk and the ftsI gene were amplified and sequenced to determine the penicillin binding protein 3 (PBP3) mutation. Molecular epidemiology was performed by MLST analyses. Results: All isolates studied were nontypeable H. influenzae (NTHi) and three of them (5.88%) caused invasive infection. The resistant rates of ampicillin and trimethoprim/sulfamethoxazole were both 45.10%. One third of these isolates produced TEM-1 type ß-lactamase and 11.76% were ß-lactamase negative ampicillin resistant strains (BLNAR). The PBP3 mutation was detected in 74.51% of the isolates, of which 12 belonged to group III. A total of 36 sequence types (STs) were identified among all isolates. Four isolates of ST103 (7.84%) all produced ß-lactamase without mutation of PBP3. Conclusion:H. influenzae infections among adults in Shanghai are predominately caused by NTHi with genetic diversity among adult patients. The prevalence of both ß-lactamase production and PBP3 mutation may contribute to high ampicillin resistance rate in Shanghai.

[Preliminary observation on imbalance degree of impedance in extracellular fluid of cells in the twelve meridians in healthy subjects].

OBJECTIVE: To calculate the imbalance degree (IBD) of left-right meridian (IBD-LRM), IBD of exterior-interior meridian (IBD-EIM) and IBD of hand-foot meridians (IBD-HFM) of impedance in extracellular fluid of cells in twelve meridians of healthy subjects, so as to provide foundation for meridian diagnosis. METHODS: A total of 31 healthy volunteers were enrolled and bioelectrical impedance spectroscopy (BIS) was applied. The constant current (from 1 to 100 kHz, 200 µA) was connected into the bilateral twelve meridians through two excitation electrodes with a distance of 10 cm. Two measuring electrodes, with an interval of 5 cm, were set in between the two excitation electrodes to collect the voltage amplitude and phase. The Cole-Cole curve fitting was used to calculate the impedance of extracellular fluid of cells in the twelve meridians; the IBD-LRM, IBD-EIM and IBD-HFM as well as their absolute values were calculated. RESULTS: The impedance of extracellular fluid in the left side was higher than that in right side in the large intestine meridian, the small intestine meridian and the bladder meridian (P<0.05, P<0.01). The mean value of IBD-LRM of extracellular fluid was (4.0±1.4) %; the mean value of absolute value of IBD-LRM was (15.0±1.1) %; the maximum absolute value of IBD-LRM was the bladder meridian. The mean value of IBD-EIM was (3.3±1.0) %; the mean value of absolute value of IBD-EIM was (17.9±1.6) %; the maximum absolute value of IBD-EIM was the bladder meridian and the kidney meridian. The impedance of extracellular fluid of hand jueyin meridian, hand taiyin meridian and hand shaoyin meridian were lower than those of foot meridians. The mean value of IBD-HFM was (-2.6±1.1) %; the mean value of absolute value of IBD-HFM was (19.7±1.7) %; the maximum absolute value of IBD-HFM was shaoyang meridian; the imbalance of yin meridians was greater than yang meridians. There were significant differences in impedance of extracellular fluid between left and right and between hands and feet (P<0.05, P<0.01). CONCLUSION: The extracellular fluid of left-right meridians of healthy subjects is different, but the absolute value of IBD is low; the mean value of exterior meridian and interior meridian is very close, and the absolute value of IBD is medium; the impedance of the foot meridians are greater than the hand meridians, and the absolute value of IBD is relatively high.

The Superior Ability of Human BDCA3+ (CD141+) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells.

Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16+, CD1c/BDCA1+, and BDCA3+ (CD141+) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3+ (CD141+) DCs have a superior capacity to stimulate allogeneic CD4+T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naïve CD4+ T cells, but contribute to their differentiation. Importantly, BDCA3+ (CD141+) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3+ (CD141+) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines.

Serotype Distribution, Antimicrobial Susceptibility, and Multilocus Sequencing Type (MLST) of Streptococcus pneumoniae From Adults of Three Hospitals in Shanghai, China.

Background:Streptococcus pneumoniae, a main causative agent associated with invasive and non-invasive infection in elderly population, is a major global health problem. After pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPV) were introduced, the distribution of S. pneumoniae serotypes has changed. There was currently limited data on epidemiology and status of antimicrobial resistance of S. pneumoniae in Shanghai. Objective: To determine the serotype distribution, antimicrobial susceptibility and molecular epidemiology of S. pneumoniae isolated from adults in Shanghai. Method: A total of 75 S. pneumoniae isolates consecutively collected from 2015 through 2017 were serotyped by conventional multiplex-PCR. The antimicrobial susceptibility was determined by broth microdilution method. The multilocus sequence type (MLST) was performed to estimate the molecular epidemiology. Results: The predominant serotypes among the isolates were 19F (20.00%), 3 (16.00%), 23F (9.33%), 14 (8.00%), and19A (5.33%). The prevalence of pneumococcal strains with serotypes targeted by vaccines PCV7, PCV10, PCV13, and PPV23 was 44, 45.33, 66.67, and 80%, respectively. Penicillin non-susceptible S. pneumoniae (PNSSP) accounted for 16% of the isolates examined and resistance to erythromycin, azithromycin, tetracycline, clindamycin, cefaclor and trimethoprim-sulfamethoxazole were found in 92.00, 90.67, 86.67, 81.33, 54.67, and 54.67% of isolates, with most isolates (78.67%) presenting multidrug-resistance. The top three sequence types (STs) were ST271 (17.33%), ST180 (9.33%), and ST81 (8.00%). The international resistance clone complexes Spain23F-1 (n = 4), Netherland3-31 (n = 8), and Taiwan19F-14 (n = 14) were identified. Conclusions: The S. pneumoniae isolates showed high genetic diversity in Shanghai and the prevalence of antimicrobial resistance was also high among S. pneumoniae isolates, most of which were multidrug-resistant. The spread of international resistance clones might contribute to the increase of resistant isolates. The PPV23 could protect against most pneumococcal capsular serotypes causing infection of adults in Shanghai.

Clinical value of MLH1-negative circulating tumor cells in lung cancer patients.

Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown.Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan-Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in lung cancer patients. Patients with lower MLH1 expression levels had worse prognoses. In a cohort of 32 randomly selected patients with lung cancer, the patients with poorer treatment responses had more MLH1-negative CTCs. The total CTCs, MLH1-negative CTCs and mesenchymal markers-expressing CTCs levels were negatively correlated with prognosis in the lung cancer patients.Our data showed the clinical significance of MLH1 expression in lung cancer tissues. The characterization and numeration of CTCs based on the expression of MLH1 and mesenchymal markers may be a convenient approach for predicting treatment response and prognosis in lung cancer.

[Comparison of Extracellular and Intracellular Fluid Distribution Between Stomach Meridian or Gallbladder Meridian and Their Neighboring Tissues of Lower Leg in Healthy Volunteers].

OBJECTIVE: To compare differences of extracellular fluid impedance (Re) and intracellular fluid impedance (Ri) between the Stomach(ST) Meridian or Gallbladder(GB) Meridian and their neighboring non-meridian sites of the left lower leg at the same level, so as to explore the distribution characteristics of body fluid in the meridian. METHODS: Sixteen healthy volunteers were enrolled in the present study. The Re and Ri were detected by using Ag/AgCl electrodes and a digital lock-in amplifier. The measuring electrodes (at an interval of about 3 cm) were separately fixed to the skin sites covering the running courses of the ST Meridian (in the lateral interspace of the anterior tibial muscle)and the GB Meridian (in the interspace of the anterior edge of the fibula), and the excitation electrodes (at an interval of about 9 cm) respectively fixed to the skin sites covering the anterior tibial muscle and the interspace between the anterior tibial muscle and the tibia (about 2 cm and 5 cm lateral to the ST and GB meridians, and about 3－4 cm and 6－8 cm lateral to the ST and GB meridians, respectively). A 100 µA constant current with frequencies from 1 kHz to 100 kHz delivered via an excitation electrode was applied to the site (control spots of the ST Meridian), and signals of the voltage amplitude and phase difference of the tissues fed to the lock-in amplifier via the measuring electrode were collected, followed by measuring those of the GB Meridian and control sites. The circumference of the lower leg around the two excitation and measuring electrodes was measured. Then the cole-cole curve fitting was performed to calculate the Ri and Re, as well as the intracellular fluid resistivity (ρi) and extracellular fluid resistivity (ρe) of the ST and GB meridians, the related muscles and interspace lateral to ST or GB (ST/GB) meridians at the same level. RESULTS: The Ri and Re (Ω) values of the ST, GB, the muscle lateral to ST/GB and the interspace lateral to ST/GB were 19.1±1.3 and 28.3±1.4, 15.8±1.9 and 25.7±2.0, 19.6±1.3 and 31.3±1.6, and 19.4±1.2 and 32.4±1.6, respectively. The Re values were significantly lower at the ST and GB meridians than at the muscle lateral to and the interspace lateral to both meridians (P<0.05). The ρi and ρe values (Ω•cm) of the ST, GB, the muscle lateral to and the interspace lateral to ST/GB were 658.9±78.5 and 953.8±75.3, 528.0±90.1 and 833.9±101.7, 669.9±71.8 and 1 059.8±86.0, 655.9±64.8 and 1 099.3±93.3, respectively. The ρi and ρe values were significantly lower at the GB Meridian Than at the other three locntions, and the ρe value of ST Meridian was significantly lower than those of the muscle lateral to and the interspace lateral to ST/GB meridians (P<0.01)．. CONCLUSION: The Ri, Re, ρi and ρe values of the ST and GB meridians are significantly lower than those of their neighboring tissues at the same levels of the lower leg, suggesting a more extracellular fluid in the meridian running course and providing evidence for our speculation that the meridian is a hydraulic resistance channel.

Understanding Qi Running in the Meridians as Interstitial Fluid Flowing via Interstitial Space of Low Hydraulic Resistance.

Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM), which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.

Antimicrobial Resistance and Molecular Characterization of Staphylococcus aureus Causing Childhood Pneumonia in Shanghai.

Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing pneumonia among children. To estimate the prevalence and molecular properties of S. aureus in children pneumonia in Shanghai, China, 107 hospitalized children with S. aureus pneumonia from two children's hospitals from January 2014 through June 2015 were studied. S. aureus isolates from the respiratory specimens were characterized by antimicrobial susceptibility, agr typing, toxin genes, multilocus sequence typing (MLST), spa, and SCCmec typing. Fifty-eight (54.2%, 58/107) were MSSA (methicillin-susceptible Staphylococcus aureus) and 49 (45.8%, 49/107) were MRSA. No isolates were found resistant to teicoplanin, sulfamethoxazole/trimethoprim, rifampicin, quinupristin/dalfopristin, linezolid, or vancomycin. However, these isolates showed high resistant rates to erythromycin, fosfomycin-trometamol and clindamycin. The agrI (87/107, 81.3%) was the most common agr allele, followed by agrIII(10/107, 9.3%), agrII(9/107, 8.4%), and agrIV(1/107, 0.9%). Six pvl-positive isolates (3 MRSA and 3 MSSA) and 7 isolates of livestock associated clone ST398 (4 MRSA, 3 MSSA) were identified. CC59 was found in 35 isolates (33 MRSA and 2 MSSA), constituting majority of MRSA (33/49, 67.35%). The dominant CC were CC59 (32.7%), CC188 (13.1%), CC7 (12.1%) and CC398 (9.3%) while t172 (16.8%), t189 (12.1%), t437 (9.3%), and t091 (9.3%) were the most common spa types. In conclusion, more particular concern should appeal to ST59-SCCmecIV-t172/t437 as it is the most common epidemic clone causing pneumonia among children in Shanghai.

[Preliminary Observation on Imbalance Degree of Blood Perfusion on the Twelve Yuan-source Points in Healthy Subjects].

OBJECTIVE: To lay a foundation for meridian diagnosis by measuring the blood perfusion (BP) on yuan-source points of twelve meridians and calculating the normal range of imbalance degree (IBD) of left and right meridian (IBD-LRM), IBD of exterior-interior meridian (IBD-EIM) and IBD of hand-foot of the same name meridians (IBD-HFM) in healthy subjects. METHODS: BP at yuan-source points of twelve meridians was measured on 31 healthy volunteers by a Laser Doppler Line Scanner (LDLS). BP distribution and IBD-LRM, IBD-EIM, IBD-HFM were calculated. RESULTS: (1) Of the twelve meridians, BP was almost equal between the left and right of the same meridian. The mean value of IBD-LRM was (0.8±7.0)%. The absolute value of IBD-LRM ranged from (13.2±12.0)% to (22.9±15.6)%, with the mean value of (16.2±4.1)%, the IBD of gallbladder meridian of foot-shaoyang was the highest. (2) Of the six pairs of exterior-interior meridians, five pairs manifested as the interior (yin) meridians being larger than the exterior (yang) meridians in BP. The mean value of IBD-EIM was (-11.4±10.4)%. The absolute value of IBD-EIM ranged from (16.6±12.1)% to (36.6±15.6)%,with the mean value of (25.2±8.0)%, the IBD between pericardium meridian of hand-jueyin and triple energizer meridian of hand-shaoyang was the highest. (3)All of the hand-foot of the same name meridians were found hand meridians being larger than foot in BP. The mean value of IBD-HFM was (38.8±18.2)%.The absolute value of IBD-HFM ranged from (34.4±20.9)% to (59.6±12.0)%, with the mean value of (43.8±13.3)%, and IBD between heart meridian of hand-shaoyin and kidney meridian of foot-shaoyin was the highest. (4) The order of IBD absolute value in BP was the same as transcutaneous CO2 emission (TCE) measured before, and their IBD-LRM absolute values were close to each other. However, the absolute values of IBD-EIM and IBD-HFM existed some differences. CONCLUSIONS: The IBD-LRM of the twelve yuan-source points in BP of healthy subjects is small and in a balance state, but IBD-EIM and IBD-HFM are relatively high.

Marked response to nab-paclitaxel in EGFR mutated lung neuroendocrine carcinoma: A case report.

RATIONALE: Lung cancer is the leading cause of cancer-related death in the world. Tyrosine kinase inhibitors (TKIs), which target mutated epidermal growth factor receptor (EGFR), have been the first-line treatment of late-stage lung adenocarcinoma harboring EGFR mutation. EGFR mutations are mostly identified in lung adenocarcinoma. However, it is rarely seen in lung neuroendocrine carcinoma, and treatment strategies remain under reported. PATIENT CONCERNS: Here, we describe a 54-year-old Chinese man diagnosed with lung adenocarcinoma (cT4N3M1b, stage IV) with neuroendocrine differentiation and L858R mutation on exon 21. He developed progressive disease in liver 4 months later, and the biopsy of liver metastases showed neuroendocrine carcinoma maintained the same EGFR mutation. DIAGNOSES: Lung adenocarcinoma and neuroendocrine carcinoma were identified by biopsy. INTERVENTIONS: After a combined treatment with nab-paclitaxel and erlotinib, the patient achieved partial remission. OUTCOMES: The patient's overall survival was 27 months. LESSONS: This case highlights that EGFR mutated lung neuroendocrine carcinoma is not responsive to single-agent EGFR-TKI. However, combined application with nab-paclitaxel can improve its efficacy and prolong the patient's survival.

Antimicrobial susceptibility and molecular epidemiology of clinical Enterobacter cloacae bloodstream isolates in Shanghai, China.

BACKGROUND: Enterobacter cloacae is a major nosocomial pathogen causing bloodstream infections. We retrospectively conducted a study to assess antimicrobial susceptibility and phylogenetic relationships of E. cloacae bloodstream isolates in two tertiary university-affiliated hospitals in Shanghai, in order to facilitate managements of E. cloacae bloodstream infections and highlight some unknowns for future prevention. METHODS: Fifty-three non-duplicate E. cloacae bloodstream isolates were consecutively collected from 2013 to 2016. Antimicrobial susceptibility was determined by disk diffusion. PCR was performed to detect extended-spectrum ß-lactamase (ESBL), carbapenemase and colistin resistance (MCR-1) gene. Plasmid-mediated AmpC ß-lactamase (pAmpC) genes were detected using a multiplex PCR assay targeting MIR/ACT gene (closely related to chromosomal EBC family gene) and other plasmid-mediated genes, including DHA, MOX, CMY, ACC, and FOX. eBURST was applied to analyze multi-locus sequence typing (MLST). RESULTS: The rates of resistance to all tested antibiotics were <40%. Among 53 E. cloacae isolates, 8(15.1%) were ESBL producers, 3(5.7%) were carbapenemase producers and 18(34.0%) were pAmpC producers. ESBL producers bear significantly higher resistance to cefotaxime (100.0%), ceftazidime (100.0%), aztreonam (100.0%), piperacillin (87.5%), tetracycline (75.0%), and trimethoprim-sulfamethoxazole (62.5%) than non-producers (p<0.05). PAmpC- and non-producers both presented low resistance rates (<40%) to all antibiotics (p>0.05). SHV (6/8, 75.0%) and MIR/ACT (15/18, 83.3%) predominated in ESBL and pAmpC producers respectively. Moreover, 2 isolates co-carried TEM-1, SHV-12, IMP-26 and DHA-1. MLST analysis distinguished the 53 isolates into 51 STs and only ST414 and ST520 were assigned two isolates of each (2/53). CONCLUSION: The antimicrobial resistance rates were low among 53 E. cloacae bloodstream isolates in the two hospitals. Multiclonality disclosed no evidence on spread of these isolates in Shanghai. The simultaneous presence of ESBL, carbapenemase and pAmpC detected in 2 isolates was firstly reported in Shanghai, which necessitated active ongoing surveillances and consistent prevention and control of E. cloacae.

The Resistance Phenotype and Molecular Epidemiology of Klebsiella pneumoniae in Bloodstream Infections in Shanghai, China, 2012-2015.

Klebsiella pneumoniae (K.pneumoniae) is a common nosocomial pathogen causing bloodstream infections. Antibiotic susceptibility surveillance and molecular characterization will facilitate prevention and management of K. pneumoniae bloodstream infections. K. pneumoniae isolates causing bloodstream infections were consecutively collected between January 2012 and December 2015 in Shanghai. Eighty isolates (20 per year) were randomly selected and enrolled in this study. Drug susceptibility were determined by the disk diffusion method. Polymerase chain reaction (PCR) was employed to detect extended-spectrum ß-lactamases (ESBLs), carbapenemases, and seven housekeeping genes of K. pneumoniae. eBURST was used for multi-locus sequence typing (MLST). More than 50% isolates were resistant to cefuroxime, ampicillin-sulbactam, and piperacillin, while carbapenems had lower resistant rates than other antibiotics. Of the 80 isolates, 22 produced ESBLs, and 14 were carbapenemase producers. In the ESBL-producing K. pneumoniae isolates, the most common ESBL genes were blaSHV and blaCTX-M. Thirteen carbapenemase producers harbored blaKPC-2 and one other carried blaNDM-5. ST11 (14/80) was the most frequent sequence type (ST), followed by ST15 (7/80) and ST29 (4/80). Our data revealed high prevalence of antibiotic resistant K. pneumoniae isolates from bloodstream infections but their genetic diversity suggested no clonal dissemination in the region. Also, one K. pneumoniae isolate harbored blaNDM-5 in this study, which was firstly reported in Shanghai.

Antimicrobial Resistance and Molecular Epidemiology of Escherichia coli Causing Bloodstream Infections in Three Hospitals in Shanghai, China.

Escherichia coli (E. coli) is one of the most frequent and lethal causes of bloodstream infections (BSIs). We carried out a retrospective multicenter study on antimicrobial resistance and phylogenetic background of clinical E. coli isolates recovered from bloodstream in three hospitals in Shanghai. E. coli isolates causing BSIs were consecutively collected between Sept 2013 and Sept 2014. Ninety isolates randomly selected (30 from each hospital) were enrolled in the study. Antimicrobial susceptibility testing was performed by disk diffusion. PCR was used to detect antimicrobial resistance genes coding for ß-lactamases (TEM, CTX-M, OXA, etc.), carbapenemases (IMP, VIM, KPC, NDM-1 and OXA-48), and phylogenetic groups. eBURST was applied for analysis of multi-locus sequence typing (MLST). The resistance rates for penicillins, second-generation cephalosporins, fluoroquinolone and tetracyclines were high (>60%). Sixty-one of the 90 (67.8%) strains enrolled produced ESBLs and no carbapenemases were found. Molecular analysis showed that CTX-M-15 (25/61), CTX-M-14 (18/61) and CTX-M-55 (9/61) were the most common ESBLs. Phylogenetic group B2 predominated (43.3%) and exhibited the highest rates of ESBLs production. ST131 (20/90) was the most common sequence type and almost assigned to phylogenetic group B2 (19/20). The following sequence types were ST405 (8/90) and ST69 (5/90). Among 61 ESBL-producers isolates, B2 (26, 42.6%) and ST131 (18, 29.5%) were also the most common phylogenetic group and sequence type. Genetic diversity showed no evidence suggesting a spread of these antimicrobial resistant isolates in the three hospitals. In order to provide more comprehensive and reliable epidemiological information for preventing further dissemination, well-designed and continuous surveillance with more hospitals participating was important.

Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.

Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK). However, the concomitant oncogenic drivers may affect the sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. Although the patient received timely and comprehensive treatment, the overall survival was only 8 months. Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may become a potential target for anti-tumor therapy.

Molecular Epidemiology of Staphylococcus aureus among Patients with Skin and Soft Tissue Infections in Two Chinese Hospitals.

BACKGROUND: Staphylococcus aureus is one of the predominant causes of skin and soft tissue infections (SSTIs), but limited data were available regarding the characterization of S. aureus from SSTIs patients in Jiangsu Province in China. We aimed to investigate the molecular epidemiology of S. aureus among SSTIs patients in two hospitals of Jiangsu Province. METHODS: Sixty-two patients with SSTIs from two Chinese hospitals in Jiangsu Province were enrolled in this study, and 62 S. aureus isolates were collected from February 2014 to January 2015. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, Staphylococcus protein A gene type, accessory gene regulator (agr) group, and Staphylococcal cassette chromosome mec t ype. RESULTS: Sixteen (25.8%) methicillin-resistant S. aureus (MRSA) isolates were detected, and there was no isolate found resistant to vancomycin, teicoplanin, sulfamethoxazole-trimethoprim, and linezolid. The sei was the toxin gene most frequently found, and no lukS/F-PV-positive isolates were detected among the SSTIs' patients. Molecular analysis revealed that ST398 (10/62, 16.1%; 2 MRSA and 8 methicillin-susceptible S. aureus) to be the dominant clone, followed by ST5 (8/62, 12.9%) and ST7 (8/62, 12.9%). CONCLUSIONS: The livestock ST398 was the most common clone among patients with S. aureus SSTIs in Jiangsu Province, China. Surveillance and further studies on the important livestock ST398 clone in human infections are necessarily requested.

Risk factors for methicillin-resistant Staphylococcus aureus carriage among residents in 7 nursing homes in Shanghai, China.

BACKGROUND: Nursing home residents are a population at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage, but few data about MRSA in this setting in Shanghai are available. The aim of this study is to determine the prevalence and risk factors for MRSA carriage in nursing home residents in Shanghai, China. METHODS: Four hundred forty-three residents from 7 nursing homes in Shanghai, China, participated in this study; nasal and axillary swabs were obtained from these residents. Laboratory identification for S aureus and antimicrobial susceptibility testing were performed when isolated. Data, including individual resident characteristics and nursing home characteristics, were collected and analyzed. RESULTS: Of the 443 participating residents, 99 (22.3%) and 45 (10.2%) residents were colonized by S aureus and MRSA, respectively. Previous hospitalization (odds ratio [OR], 2.564; 95% confidence interval [CI], 1.214-5.415; P = .014), presence of an invasive device (OR, 3.455; 95% CI, 1.678-7.113; P = .001), chloramphenicol therapy (OR, 7.672; 95% CI, 1.807-32.580; P = .006), and macrolides therapy (OR, 2.796; 95% CI, 1.056-7.403; P = .038) were independent risk factors for MRSA colonization. Low expenditure per month and less good sanitary condition also increased the risk for MRSA colonization. CONCLUSIONS: Our study suggests that nursing homes are significant reservoirs for MRSA. Implementation of infection control strategies must be given high priority in nursing homes to fight the high prevalence of MRSA, and increased convenience and feasibility should also be realized with these control strategies for MRSA colonization.

Prevalence and Molecular Epidemiology of Staphylococcus aureus among Residents of Seven Nursing Homes in Shanghai.

BACKGROUND: Residents in nursing homes (NHs) always represent potential reservoirs for Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). To our knowledge, there is no epidemiological information up till now that describes the prevalence and molecular characteristics of S. aureus in nursing home residents in Shanghai, China. METHODS: Four hundred and ninety-one unique residents from 7 NHs were enrolled in this study. Specimens were collected among these residents including 491 nasal swabs, 487 axillary swabs and 119 skin swabs. S. aureus isolated and identified from the swabs was characterized according to antimicrobial susceptibility profiling, toxin gene prevalence, and multilocus sequence typing (MLST), spa and SCCmec typing. RESULTS: Among the 491 residents screened, S. aureus was isolated in 109 residents from 90 nasal swabs (90/491, 18.3%), 29 axillary swabs (29/487, 6.0%), and 22 skin swabs (22/119, 18.5%). Sixty-eight MRSA isolates were detected in 52 residents from 41 nasal carriers, 15 axillary carriers and 12 skin carriers. The overall prevalence rate of S. aureus and MRSA colonization was 22.2% and 10.6% respectively. Ten residents presented S. aureus in all three sample types and 12 residents presented S. aureus in two of the three sample types collected. Molecular analysis revealed CC1 (29.1%) to be the dominant clone in this study, followed by CC398 (19.9%), CC188 (13.5%) and CC5 (12.8%). The most common spa type was t127 (22.0%), followed by t14383 (12.8%) and t002 (10.6%). CONCLUSIONS: A high prevalence of S. aureus and MRSA colonization was revealed in nursing home residents in Shanghai. CC1 was the most common clonal complex and t127 was the most common spa type among NH residents. The data provides an important baseline for future surveillance of S. aureus in NHs in Shanghai and other highly urbanized regions in China. Implementation of infection control strategies must be given high priority in NHs to fight such high prevalence of both MRSA and methicillin-susceptible S. aureus (MSSA).