Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways-inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER's protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

[Comparison of Malaria Diagnosis between County and Provincial Laboratories in Guizhou Province].

Malaria cases reported by county laboratories were further tested in the provincial laboratory in Guizhou province by using PCR test and microscopy. The consistency between PCR and microscopic results in the provincial laboratory was set as the basis for evaluation of microscopic results in county laboratories. In 89 samples, 24 were identified by PCR to be positive for malaria, among which 15 were infected with P. falciparum, 7 with P. vivax, and 2 with P. ovale; all were imported cases. And 21 samples had consistent identifications by PCR test and microscopic examination in the provincial laboratory. The total coincidence rate between county and provincial laboratories was 79.8%(67/84), and the undetected and error rates in county laboratories were 9.5%(2/21) and 23.8% (15/63), respectively. The Kappa value between county and provicial diagnosis was 0.6, being at the medium-to-high level of consistency.

[Single-tube Single-run Multiplex PCR Detects Mixed Samples with Four Species of Plasmodium].

OBJECTIVE: To establish a single-tube single-run multiplex PCR technique that can detect single or mixed samples with four species of Plasmodium. METHODS: Folding primers were designed based on the fast nested PCR. The reaction component concentrations were optimized and the primers were selected based on the annealing temperature. The established single-tube single-run folding-primer multiplex PCR (FP-PCR) was tested for its sensitivity and specificity to detect single-species and mixed samples with P. vivax, P. falciparum, P. ovale (including P. ovale wallikeri) and/or P. malariae. RESULTS: In all the seven experimental repeats, FP-PCR successfully detected single-species infection for all the four species, with the detection limit reaching or close to 1 parasite/µl blood. For mixed infections with 2-4 species at different densities with the highest being 100 times of the lowest, FP-PCR identified all the species in each combination in 57 out of 84 tests. Further, in 10 dried blood samples on filter paper from healthy subjects, no FP-PCR amplification was found, except weak formation of dimers. CONCLUSION: FP-PCR is a simple and sensitive method for detecting both single-species and mixed infections with human Plasmodium, and can be applied for malaria diagnosis, screening and monitoring.

Association between serum cotinine and hepatic steatosis and liver fibrosis in adolescent: a population-based study in the United States.

Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12-19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [ß = 0.41 (0.07, 0.76), p = 0.018] and 0.05-2.99 ng/ml [ß = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

[Assessment of prognostic and influencing factors in elderly patients with multiple organ dysfunction syndrome].

OBJECTIVE: To preliminarily assess the prognosis of patients with multiple organ dysfunction syndrome (MODSE) and analyze their influencing factors. METHODS: The clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital during January 2009 to June 2012 were analyzed retrospectively. According to 28-day outcomes, they were divided into 2 groups (28-day survival and non-survival) while 4 groups according to age. Then these prognosis were evaluated with the current scoring systems ((acute physiology and chronic health evaluation II (APACHEII and III), sample acute physiological score (SAPSII) and multiple organ dysfunction score (MODS)). The predictive powers were compared by receiver operating characteristic (ROC) curve. Finally a binary Logistic regression analysis was performed to evaluate the relevant influencing prognostic factors of MODSE. RESULTS: The mean age was (77.8 ± 9.1) years, mean number of failed organs (3.6 ± 1.2) and a 28-day mortality 45.8%. The ages of non-survival group were older than those of survival group ((78.1 ± 9.1) vs (76.7 ± 11.0) years). The number of organ failures ((4.3 ± 1.1) vs (3.1 ± 1.0)) and scores (APACHEII: (28 ± 7) vs (20 ± 8), APACHE III: (106 ± 27) vs (75 ± 31), SAPSII: (64 ± 16) vs (46 ± 18), MODS: (9 ± 3) vs (6 ± 3)) of non-survivals were significantly higher than that of survivals. The area under ROC curve of these four score systems were 0.790, 0.781, 0.780 and 0.780 respectively. Compared to the above systems, SAPSII had the best performance in sensitivity while APACHEII was more valuable in specificity. All clinical data underwent binary Logistic regression and the results showed that plasma concentration of albumin and mean arterial pressure (MAP) offered beneficial outcomes while age and number of organ failures had unfavorable prognosis. The greater patient age, the higher their mortality. CONCLUSIONS: All four scoring systems have accurate prognostic predictions of MODSE patients. And the predictive power of APACHEII is the best. Plasma concentration of albumin, MAP, age and organ failure number are independent prognostic factors in MODSE patients.

[A clinical analysis of 7 cases of allergic bronchopulmonary aspergillosis].

OBJECTIVE: To study the clinical features, diagnosis and treatment of allergic bronchopulmonary aspergillosis (ABPA). METHODS: The clinical presentations, serologic results, chest radiology, pathological results and treatment of 7 patients with ABPA in Chinese PLA General Hospital were retrospectively analyzed. RESULTS: There were 4 males and 3 females, with a mean age of (33 ± 16) years. Before the diagnosis of ABPA, 6 cases had been misdiagnosed as bronchial asthma, 3 as pulmonary infection, 2 as tuberculosis and 1 as bronchiectasis. The main clinical manifestations included cough (n = 6), sputum production (n = 5), hemoptysis (n = 4), wheeze (n = 3), dyspnea(n = 3) and fever(n = 2). All cases had increased total serum IgE levels (median 3040 U/ml) and peripheral blood eosinophil count (median 0.19). Six of them showed increased peripheral eosinophil count median 1.84 × 10(9)/L, and skin test positive for Aspergillus antigen. Five of them had increased serum IgE antibodies specific to A. fumigatus (22 ± 15) kU/L, and 4 had increased serum IgG antibodies specific to A. fumigatus (108 ± 96) mg/L. The chest CT scan findings included transient or fixed pulmonary opacities, central bronchiectasis and finger-in-glove opacities. Five patients were treated with corticosteroids combined with antifungal therapy. CONCLUSIONS: Clinical features of ABPA include a history of asthma, elevation of the total serum IgE levels, presence of aspergillus IgE antibodies, peripheral eosinophilia, and transient or fixed pulmonary opacities and central bronchiectasis. Patients with asthma complicated with bronchiectasis should be routinely screened for Aspergillus skin test, and measurement of total serum IgE levels and chest CT scan are useful for confirmation of the diagnosis of ABPA. Oral glucocorticoids and anti-fungal drugs are effective in treatment of ABPA. Regular follow-up is needed for prevention of recurrence.

[Adult hospital acquired pneumonia: a multicenter study on microbiology and clinical characteristics of patients from 9 Chinese cities].

OBJECTIVE: To investigate the etiology and clinical characteristics of hospital-acquired pneumonia (HAP) in China and to provide evidence for appropriate therapy. METHODS: We performed a prospective multicenter study in 13 Chinese urban tertiary hospitals. All HAP cases diagnosed at respiratory general ward and respiratory intensive care unit (RICU) from August 2008 to December 2010 were studied. Epidemiological data, etiology and clinical characteristics of enrolled patients were collected. Sputum or tracheal aspirate and blood cultures, Legionella antibodies and Streptococcus pneumoniae urinary antigen tests were performed. Bacteria to antimicrobial susceptibility test was performed. RESULTS: A total of 610 cases of HAP were diagnosed during the study, with an overall incidence of 1.4% among 42 877 hospitalized patients, while the incidence was 0.9% (362/41 261) in respiratory general ward and 15.4% (248/1616) in RICU. 93.9% (573 cases) of patients had at least one underlying disease, and 91.0% (555 cases) had exposure to at least one antimicrobial agent within 90 days prior to HAP diagnosis. Pathogens were identified in 487 patients, with Acinetobacter baumannii [30.0% (183/610)], Pseudomonas aeruginosa [22.0% (134/610)], Staphylococcus aureus [13.4% (82/610)] and Klebsiella pneumonia [9.7% (59/610)] being the most common pathogens. Eighteen patients (3.0%) had infection with fastidious bacteria. A. baumannii and S. aureus were the more frequent pathogens in the ventilator-associated pneumonia (VAP) cases [50.5% (97/192) and 21.4% (41/192)] as compared to non-VAP cases [20.6% (86/418) and 9.8% (41/418), P < 0.01]. A. baumannii and S. aureus were also frequent pathogens in cases with a score of more than 20 by the acute physiology and chronic health evaluation II (APACHEII) scoring [45.7% (69/151) and 20.5% (31/151)], as compared to cases with a score of less than 20 of APACHE II [24.8% (114/459) and 11.1% (51/459), P < 0.01]. A. baumannii showed high resistance rates to carbapenems [more than 70% (109/142)], and the susceptibility to cefoperazone/sulbactam, polymyxin B and tigecycline were 40.8% (58/142), 99.3% (141/142) and 95.8% (136/142) respectively. Resistance rates of P. aeruginosa to meropenem and imipenem were 48.8% (40/82) and 70.7% (58/82) respectively. Methicillin-resistant S. aureus (MRSA) accounted for 87.8% (43/49) in all strains of S. aureus. Mortality rate of VAP cases was 34.5% (61/177), significantly more than that of HAP patients [22.3% (135/605), P < 0.05]. The average hospital stay of patients with HAP was (23.8 ± 20.5) days, significantly more than that of the average for inpatients [(13.2 ± 13.6) days, P < 0.01] during the study period. Mean costs of HAP were (108 950 ± 116 608) yuan, significantly higher than the average hospital costs of respiratory inpatients (17 999 ± 33 364) yuan. CONCLUSIONS: Among Chinese patients hospitalized in urban tertiary medical centers, HAP incidence and mortality rate were high, which increased the patients' hospital stay and the medical costs. Common pathogens were A. baumannii, P. aeruginosa, S. aureus and K. pneumonia. The common bacteria of HAP in China showed high resistance rates to antibiotics.

[HPLC fingerprint of citri grandis exocarpium from different cultivars].

OBJECTIVE: To study the quality difference among Citrus grandis 'Tomentosas' of different cultivars, in order to provide scientific basis for seeking for fine breeds. METHOD: The HPLC fingerprints were established for C. grandis 'Tomentosa' of different cultivars in the GAP base of Huazhou Green Life Co., Ltd. The software of similarity evaluation system of traditional Chinese medicine HPLC fingerprints 2004A edition of Chinese Pharmacopoeia Commission was adopted for the similarity analysis and judgment of cultivars. RESULT: The fingerprints showed similar general characteristics of samples of different cultivars. Specifically, the similarity of areas of the 18 common peaks ranged between 0.938-0.998. The success rate of judging cultivars using similarity software stood at 92%. CONCLUSION: This method can be applied to better identify quality and source of cultivars of C. grandis 'Tomentosa', and provide technical measures and scientific basis for seeking for fine breeds of Citri Grandis Exocarpium.

RNA profiling of blood platelets noninvasively differentiates colorectal cancer from healthy donors and noncancerous intestinal diseases: a retrospective cohort study.

BACKGROUND: The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases. METHODS: Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn's disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed. RESULTS: TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set. CONCLUSIONS: RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance.

A clinical study on the effects and mechanism of xuebijing injection in severe pneumonia patients.

OBJECTIVE: To observe the effects of Xuebijing Injection in patients with severe pneumonia, and to explore the mechanism. METHODS: Eighty cases of severe pneumonia are randomly assigned to the Xuebijing treatment (forty cases) and the control group (forty cases), with the same routine therapy provided in both groups. Clinical effective rates, inflammatory factors and organ function were observed in both groups. RESULTS: The effective rate was higher in Xuebijing group than that of the control group (80.0% vs. 67.5%, P < 0.05). As compared with the control group, the LDH, alpha1-AG, alpha1-AT levels and the peak body temperature decreased markedly with the Xuebijing treatment going, and the secretion of TNF-alpha, IL-6, IL-8 was suppressed in Xuebijing group; but no significant difference was found in leptin level. CONCLUSION: Xuebijing Injection may show a protective effect in patients with severe pneumonia. The mechanism is possibly with the decreased secretion of TNF-alpha, IL-6, and IL-8.

[A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007].

OBJECTIVE: To investigate the pathogens, clinical manifestations, prognosis of and the risk factors for pulmonary mycosis in China. METHODS: All cases of pulmonary mycosis from 16 centers in 10 cities from Jan. 1998 to Dec. 2007 that met the diagnostic criteria were included for clinical, microbiological and radiological analysis. RESULTS: Totally 474 cases of pulmonary mycosis were retrieved. The top 5 pulmonary mycosis was pulmonary aspergillosis (180 cases, 37.9%), pulmonary candidiasis (162 cases, 34.2%), pulmonary cryptococcosis (74 cases, 15.6%), pneumocystis carinii pneumonia (23 cases, 4.8%) and pulmonary mucormycosis (10 cases, 2.1%). The constituent ratio in the last 3 years was similar to that in the former 7 years. The main pathogens of pulmonary candidiasis were Candida albicans (308/474, 65.0%) and Candida tropicalis (57/474, 12.0%), which were sensitive to common azoles. Compared with bacterial pneumonia, pulmonary mycosis showed more symptoms of hemoptysis (147/474, 31.0%) and pleural effusion (95/474, 20.0%), and less radiological specificity. Classical halo sign (4/474, 0.8%) and crescentic sign (17/474, 3.6%) were only shown in several cases of pulmonary mycosis. The most common underlying diseases were tumor (including solid tumor and malignant hematological diseases) (94/474, 19.8%), chronic obstructive pulmonary disease (52/474, 11.0%), pulmonary tuberculosis (50/474, 10.5%) and diabetes (48/474, 10.1%). Compared with the other common pulmonary mycosis, pulmonary cryptococcosis affected younger patients, and more cases were community-acquired, but fewer cases with underlining diseases or compromised immune function, and had a better prognosis. CONCLUSION: The ahead five species of pulmonary mycosis in China were orderly pulmonary aspergillosis, pulmonary candidosis, pulmonary cryptococcosis, pneumocystis carinii pneumonia and pulmonary mucormycosis. The main pathogens of pulmonary candidosis were Candida albicans and Candida tropicalis, which were sensitive to common azoles. Compared with the other common pulmonary mycosis, pulmonary cryptococcosis catch younger patients, had more community-acquired cases, and had better prognosis.

[Antimicrobial resistance and genotyping of Acinetobacter baumannii in ICU].

OBJECTIVE: To investigate the outbreak of acinetobacter baumannii in the ICU, and to explore the antimicrobial resistance characteristics of pathogens, and therefore to determine the optimal prevention strategies. METHODS: From May to June 2007, most of the cases of infection by acinetobacter baumannii in our ICU were collected. PFGE (pulsed field gel electrophoresis) and standard disk diffusion susceptibility tests were performed on the strains isolated from the patients' body fluids including sputum, blood, urine, secretion and from the ICU environment involving the patients' bed sheet, skin surface and medical staff's hands, humidification water of ventilator tubes. RESULTS: Twelve strains were resistant to imipenem and meropenem. Colistin sulphate and tigecycline showed a high rate of antimicrobial activity against the strains, the rate of susceptibility being 100% and 91.7% respectively. These strains belonged to 3 clones (clone A, B, C) and there were 2 sub-clones (A1, A2) belonging to clone A. The sub-clone A1 was isolated from the surface of unwashed medical staff's hands and patients' body fluids. From intermediate to resistance, the antimicrobial characteristics of clone A and clone B to minocycline changed over a month, and there was one strain that was resistant to tigecycline. CONCLUSION: The outbreak of acinetobacter baumannii in the ICU was caused by carbapenem resistant acinetobacter baumannii (CRAb). The delicate changes of disk diffusion susceptibility in clones A and B occurred in one month. Unwashed hands of medical staff were probably responsible for the outbreak.

Eating Centipedes Can Result in Angiostrongylus cantonensis Infection: Two Case Reports and Pathogen Investigation.

Angiostrongyliasis is a food-borne parasitic disease caused by the nematode Angiostrongylus cantonensis that can lead to eosinophilic meningitis (EM) or meningoencephalitis in humans. Angiostrongylus cantonensis is prevalent in the Pacific Islands. In recent years, a large number of outbreaks and severe cases have occurred. Several species of mollusk, such as snails and slugs, act as intermediate and paratenic hosts of A. cantonensis. In this study, two cases of EM were found to have been caused by infection with A. cantonensis due to consumption of raw centipedes. To survey the A. cantonensis infections acquired through centipedes that the patients had bought at a vegetable market, we performed etiological examinations and polymerase chain reaction amplification of A. cantonensis genes. Third-instar larvae of A. cantonensis were detected in the centipedes, and specific genes from A. cantonensis were detected in all the specimens. This indicates that the centipede may act as a competent host for the transmission of A. cantonensis. To our knowledge, this is the first report of A. cantonensis infection through the consumption of centipedes.

Infection by the nematode Angiostrongylus cantonensis induces differential expression of miRNAs in mouse brain.

BACKGROUND: The parasitic nematode Angiostrongylus cantonensis is the primary pathogen causing eosinophilic meningitis and meningoencephalitis in nonpermissive hosts. The larval parasites are eliminated by the host's immune responses in the central nervous system (CNS) through infiltration of eosinophils and lymphocytes. This study aimed to determine primary alterations of microRNA (miRNA) during A. cantonensis infection in mice. METHODS: miRNA array was used to analyze the expression of miRNA in uninfected and A. cantonensis-infected mouse brains at 21 days postinfection (dpi). Target genes were predicted by miRDB software, and protein-protein interaction network was analyzed using STRING v9.1. Expression levels of selected miRNAs and cytokine production were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Twenty-five mature miRNAs showed differential expression in infected mouse brains, of which 24 were upregulated and one was downregulated compared to the uninfected control. These 25 miRNAs were divided into five clusters, and the first upregulated cluster was selected for further bioinformatics analysis. Target gene prediction and gene ontology (GO) enrichment analysis revealed that the miRNAs were mainly related to the immune response. Furthermore, six target genes of mmu-miR-146a-5p were predicted to interact with tumor necrosis factor alpha (TNF-α). The in vitro study suggested that transfected mmu-miR-146a-5p inhibitor upregulated TNF-α and its target gene Traf6 in microglia following stimulation with A. cantonensis larval antigen. CONCLUSION: This study suggested a critical role of miRNAs in the host defense during A. cantonensis infection, providing new insights into the molecular mechanisms underlying the interaction between mmu-miR-146a-5p and TNF-α in angiostrongyliasis in nonpermissive hosts.

Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.

Community-acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

Proteomic Analysis of Differentially Expressed Proteins in Intracranial Angiostrongylus cantonensis Larvae in Permissive and Non-Permissive Hosts.

Angiostrongylus cantonensis infection can lead to severe neuropathological damage caused by the development of these nematodes in the central nervous system after penetrating the blood-brain barrier. They commonly cause eosinophilic meningitis or meningoencephalitis in non-permissive hosts (e.g., mice). It has been shown that differences exist in the brains of permissive and non-permissive hosts during the larval development of A. cantonensis; however, the mechanism underlying the difference is not completely understood. This study analyzed and characterized the differentially expressed proteins in the intracranial A. cantonensis larvae in rat (ILR) and mouse (ILM) brains by using proteomics. We found that 29 proteins were differentially expressed: 12 of these proteins were highly expressed in ILR, whereas the remaining 17 proteins were highly expressed in ILM. Three protein spots were homologous to the actin-2, actin-1, and disorganized muscle protein 1 (dim-1) of Caenorhabditis elegans. In addition, proteomic analyses revealed that act-1 and act-2 were up-regulated in ILM compared to ILR, whereas dim-1 was down-regulated in ILM. Annotation using gene ontology revealed that act-1, act-2, and dim-1 were mainly associated with adenosine triphosphate (ATP) catabolic processes and ATP binding. Quantitative real-time polymerase chain reaction analyses of act-1 and dim-1 using the first internal transcribed spacers of A. cantonensis 18S ribosomal RNA (rRNA) was consistent with 2-dimensional gel electrophoresis (2-DE) and the sizes of these parasites; ILR was longer and wider than ILM. These results indicate that the differentially expressed proteins dim-1 and act-1 could be related to the development and pathogenicity of A. cantonensis in different hosts.

Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study.

BACKGROUND: Drug resistant Mycoplasma pneumoniae (MP) is a rising issue in the management of community-acquired pneumonia (CAP). Epidemiological monitoring is essential for identifying resistant patterns of MP isolates against various antibiotics in adult CAP patients. METHODS: This is a prospectively designed multicenter study conducted on adult patients with CAP visiting six teaching hospitals in the cities of Beijing, Shanghai and Guangzhou between September 2010 and June 2012. RESULTS: A total of 520 adult patients (mean age: 45.7±26.2 years) with CAP visiting teaching hospitals in the cities of Beijing, Shanghai and Guangzhou were included. Of the 520 patients, only 75 (14.42%) were confirmed MP positive by means of culture and real-time PCR methods. Quinolones were the most common initially prescribed antimicrobial, followed by ß-lactams and ß-lactams plus quinolones. Macrolide resistance was as high as 80% and 72% against erythromycin (ERY) and azithromycin (AZM) respectively, which were associated with the A2063G transition mutation in domain V of the 23S ribosomal RNA (rRNA) gene. Six strains with mild to moderate ERY-resistant level were still susceptible to AZM. Tetracycline (TET), minocycline (MIN) and quinolones [moxifloxacin (MOX) and fluoroquinolones] had no signs of resistance. CONCLUSIONS: High resistance was observed with macrolides, whereas, none of the MP strains were resistant to fluoroquinolones and TET. Hence, macrolide resistant MP (MRMP)_infections could be well treated with fluoroquinolones. However, few isolated strains had minimal inhibitory concentration (MIC) values on the edge of resistance to quinolones, alarming a quinolone-resistant MP in the near future.

[Expression of high-level cephalosporinase due to mutation in the AmpC attenuator of a clinical Escherichia coli strain].

OBJECTIVE: To study the resistant phenotype of a clinical strain of Escherichia coli and to explore the effect of its attenuator mutation on AmpC expression. METHODS: A clinical strain of Escherichia coli 20022 (ECO20022) resistant to cefoxitin was isolated clinically. The phenotype was examined by three-dimensional methods, isoelectric focusing (IEF), and microdilution method. The regulator genes of ECO20022 were amplified and sequenced, and the difference between them was analyzed by BLAST method. Then the regulator genes were cloned into pCAT3-basic vector (a promoterless reporter gene vector). Microdilution method was used to detect the minimal inhibitory concentration (MIC) of chloramphenicol and ampicillin to this strain with E. coli ATCC25922 as quality control bacterium. ELISA was used to detect the content of chloramphenicol acetyl transferase (CAT). RESULTS: Compared to the standard E. coli K-12, there were four base substitutions, i.e., 22C-T, 26, 27TA-GT, and 32G-A in the attenuator region of ECO20022. Three-dimensional method showed that this strain was high AmpC-producing. IEF found that it produced three beta-lactamases with the values of PI of 5.4, 8.2, and 9.0 respectively. The beta-lactamase with the PI of 9.0 could be inhibited by cloxacillin but not by clavulanate. The strain was resistant to not only most of third generation cephalosporins, but also to cefepime; however it was still susceptible to carbapenem. The secondary structure of the attenuator RNA of ECO20022 was different from the traditional structure of E. coli K-12. The regulator gene was successfully cloned into pCAT3-basic vector and direct and indirect tests indicated that this regulator gene enhanced the CAT expressing level as much as 10 times that of Escherichia coli K-12. CONCLUSION: AmpC attenuator mutation leads to high AmpC expression in Escherichia coli, resulting in a significant rise of resistance level to beta-lactamase and a great menace to clinical antibiotic therapy.

[Efficacies of ceftazidime and cefepime in rats with experimental pneumonia caused by extended-spectrum beta-lactamase-producing strain of Klebsiella pneumonia].

OBJECTIVE: To investigate the in vivo activities of ceftazidime and cefepime with susceptibility in vitro in rats with experimental pneumonia caused by extended-spectrum beta-lactamase-producing strain of Klebsiella pneumonia. METHODS: With intratracheal instillation method, 3 Klebsiella pneumonia strains isolated from this hospital were used to produce 3 groups of experimental model of pneumonia in rats. All the 3 strains showed resistant to cefotaxime and susceptible to piperacillin-tazobactam in vitro. To ceftazidime and cefepime, strain 1 was both susceptible. Strain 2 was susceptible to ceftazidime and resistant to cefepime. Strain 3 was resistant to ceftazidime and susceptible to cefepime. The three groups of rats were randomly assigned to one of the following five groups: one control group and four treatment groups. The efficacies were evaluated 96 hours later by the survival rate and the viable bacterial counts of the lungs (lg CFU/g). RESULTS: Group 1: piperacillin-tazobactam, ceftazidime and cefepime significantly improved the survival rate (75.0%, 76.9%, 80.0%) and reduced the bacterial counts [(10.8 +/- 2.8), (11.1 +/- 3.2), (11.0 +/- 3.7) lg CFU/g] compared with cefotaxime and the control group [36.0%, 32.0%; (15.7 +/- 5.6), (16.0 +/- 5.5) lg CFU/g; P < 0.05]. Group 2: piperacillin-tazobactam, ceftazidime significantly improved the survival rate (79.2%, 73.1%) and reduced the bacterial counts [(10.7 +/- 2.3), (11.0 +/- 2.7) lg CFU/g] compared with cefotaxime and the control groups [42.3%, 33.3%; (15.5 +/- 5.4), (15.8 +/- 4.6) lg CFU/g; P < 0.05]. Group 3: the survival rate in piperacillin-tazobactam and cefepime groups (80.8%, 75.0%) were significantly higher and the bacterial counts in piperacillin-tazobactam [(10.4 +/- 2.4) lg CFU/g] were significantly lower compared with the cefotaxime and the control groups [37.5%, 34.6%; (14.2 +/- 5.6), (15.3 +/- 4.9) lg CFU/g; P < 0.05]. CONCLUSION: Cefepime and ceftazidime can reduce the mortality and the number of viable bacteria in rat pneumonia caused by some ESBL-producing Klebsiella pneumonia strains susceptible to either of them and their efficacies were similar to piperacillin-tazobactam.