ABSTRACT
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Subject(s)
Blood Platelets , Ovarian Neoplasms , Humans , Female , Blood Platelets/pathology , Biomarkers, Tumor/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , ChinaABSTRACT
Various predictive biomarkers are needed to select candidates for optimal and individualized treatments. Tumor-infiltrating immune cells have gained increasing interest in cancer research for the prediction of therapeutic response and survival. However, the role of dendritic cells (DCs) in PD-1 blockade immunotherapy remains unclear. In this study, we identified a population of PD-1+ DCs in the tumor microenvironment (TME) of cervical cancer (CC). The accumulation of PD-1+ DCs in cervical tumors was correlated with advanced stages, elevated preoperative squamous cell carcinoma antigen levels and lymph-vascular space invasion. PD-1 expression was induced on activated tumor-associated DCs (TADCs) in vitro compared with their resting counterparts. This PD-1+ DC population was characterized by reduced secretion of cytokines (IL-12, TNF-α, and IL-1ß) and dysfunctional induction of T cell proliferation and cytotoxic reaction. PD-1 blockade significantly reinvigorated PD-1+ DCs to release IL-12, TNF-α, and IL-1ß compared with PD-1- DCs. TILs from samples with higher PD-1+ DC infiltration could be induced to achieve a greater killing effect of PD-1 blockade treatment. Our findings suggested a role for PD-1+ DCs in immune surveillance dysfunction and CC progression. PD-1+ DC density in the TME may serve as a diagnostic factor for predicting the optimal beneficiaries of PD-1/PD-L1 blockade immunotherapy in CC.
Subject(s)
B7-H1 Antigen , Uterine Cervical Neoplasms , Dendritic Cells/metabolism , Female , Humans , Immune Checkpoint Inhibitors , Immunotherapy , Interleukin-12/metabolism , Programmed Cell Death 1 Receptor , Tumor Microenvironment , Tumor Necrosis Factor-alpha/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/therapyABSTRACT
The interactions between Emiliania huxleyi and E. huxleyi virus (EhV) regulate marine carbon and sulfur biogeochemical cycle and play a prominent role in global climate change. As a large DNA virus, EhVs have developed a novel "virocell metabolism" model to meet their higher metabolic needs. However, the regulatory mechanism of this metabolic model is still largely unclear. MicroRNAs (miRNAs) can regulate biological pathways through targeting hub genes in the metabolic processes. Here, we performed high-throughput small RNA sequencing to analyse miRNA expression in EhV99B1 infected E. huxleyi BOF92. A total of 26 miRNAs (including 2 virus-derived miRNAs) were identified, including four up-regulated and one down-regulated miRNAs. These results were further validated through quantitative real-time PCR. Functional enrichment analysis showed that five differentially-expressed miRNAs might be involved in the regulation of carbohydrate metabolism, lipid metabolism and amino acid metabolism. Moreover, the expression levels of differentially-expressed miRNAs were negatively correlated with that of several lipid metabolism-related genes, such as ACC-1, SPT, ACOX, ACAT, CERS and ACADS, indicating that these miRNAs might play an important regulatory role in virus-mediated lipid metabolism.
Subject(s)
Haptophyta , MicroRNAs , Virus Diseases , Viruses , Haptophyta/genetics , Haptophyta/virology , MicroRNAs/genetics , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer. METHODS: We performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups. RESULTS: A total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes. CONCLUSION: Peripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.
ABSTRACT
Polysaccharides from red algae Porphyra haitanensis and Gracilaria lemaneiformis possess various bioactive functions, however, their anti-diarrhea activity remains incompletely defined. In the current study, sulphated polysaccharides were extracted by high pressure treatment plus ethanol precipitation from these two algae, and named PHSP(hp) and GLSP(hp), respectively. PHSP(hp) and GLSP(hp) showed decreased viscosity and molecular weight. Meanwhile, they have a certain immunomodulatory effect on wound healing and migration of RAW264.7 cells. Moreover, they significantly increased the secretion of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). A BALB/c model infected by enterotoxigenic Escherichia coli (ETEC)-K88 was also established to evaluate the anti-diarrhea activity of PHSP(hp) and GLSP(hp). The results showed that PHSP(hp) and GLSP(hp) were able to alleviate mice diarrhea symptoms. Meanwhile, they inhibited the release of pro-inflammatory cytokines and suppressed the secretion of immunoglobulin A via reducing the population of B cells. In addition, the nitroblue tetrazolium levels of mouse serum were decreased. Taken together, PHSP(hp) and GLSP(hp) alleviated the inflammatory response of ETEC-K88-induced diarrhea through both specific and non-specific immunity. Sulphated polysaccharides from red algae may be used as functional food components for remitting diarrhea.
ABSTRACT
To investigate the clinical course and management of congenital vaginal atresia. This retro-spective analysis included patients with congenital vaginal atresia treated from March 2004 to August 2014 at the Obstetrics and Gynecology Hospital of Fudan University. Thirty-nine patients were included in this study. Their average age was 16.87±2.2 years when they came to our hospital. Totally, 51% of the patients had isolated congenital vaginal atresia with a normal cervix, whereas the others had either cervical atresia or imperforate hymen. The primary presenting signs and symptoms included primary amenorrhea (71.8%), periodic abdominalgia (41.0%), abdominal pain (36.0%), dyspareunia (10.3%), menstrual disorders (5.1%), and pelvic mass (5.1%). Ultrasound and magnetic resonance imaging (MRI) were effective inspection methods for the screening of urogenital tract-associated anomalies. Vagi-noplasty mainly included simple vagina reconstruction with insertion of a mold (n=22) and split-thickness skin grafting (n=4). In 64% of surgical patients, normal menstrual bleeding was achieved. Four of the patients subsequently became pregnant and delivered at term. Primary amenorrhea, periodic abdominalgia and abdominal pain are the main reasons for the post pubertal patients to visit doctors. Surgical methods can successfully provide these patients an opportunity for subsequent conservative management, can result in normal menstrual bleeding, resolve cyclic pelvic pain, and provide some po-tential for fertility.
Subject(s)
Abdominal Pain/surgery , Amenorrhea/surgery , Dyspareunia/surgery , Hymen/abnormalities , Menstruation Disturbances/surgery , Plastic Surgery Procedures/methods , Vagina/surgery , Abdominal Pain/physiopathology , Abdominal Pain/rehabilitation , Adolescent , Amenorrhea/physiopathology , Amenorrhea/rehabilitation , Congenital Abnormalities , Dyspareunia/physiopathology , Dyspareunia/rehabilitation , Female , Fertilization/physiology , Humans , Hymen/surgery , Menstruation/physiology , Menstruation Disturbances/rehabilitation , Recovery of Function , Vagina/abnormalities , Young AdultABSTRACT
Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure. In simulated gastric fluid digestion, TIM can be degraded into small fragments, while retaining over 80% of the IgE-binding activity. The full-length cDNA of O. fangsiao TIM (1140bp) was cloned, which encodes 247 amino acid residues, and the entire recombinant TIM was successfully expressed in Escherichia coli BL21, which showed similar immunoreactivity to the native TIM. Different intensity of cross-reactivity among TIM from related species revealed the complexity of its epitopes. Eight linear epitopes of TIM were predicted following bioinformatic analysis. Furthermore, a conformational epitope (A71G74S69D75T73F72V67) was confirmed by the phage display technology. The results revealed the physicochemical and immunological characteristics of TIM, which is significant in the development of hyposensitivity food and allergy diagnosis.
Subject(s)
Allergens/immunology , Epitopes, B-Lymphocyte/immunology , Octopodiformes/enzymology , Octopodiformes/immunology , Triose-Phosphate Isomerase/immunology , Adolescent , Adult , Allergens/chemistry , Allergens/genetics , Amino Acid Sequence , Animals , Child , Cloning, Molecular , Cross Reactions , Electrophoresis, Gel, Two-Dimensional , Epitope Mapping , Female , Food Hypersensitivity/etiology , Food Hypersensitivity/immunology , Humans , Immunoblotting , Male , Middle Aged , Models, Molecular , Octopodiformes/chemistry , Octopodiformes/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Triose-Phosphate Isomerase/chemistry , Triose-Phosphate Isomerase/genetics , Young AdultABSTRACT
To investigate the clinical course and management of congenital vaginal atresia.This retrospective analysis included patients with congenital vaginal atresia treated from March 2004 to August 2014 at the Obstetrics and Gynecology Hospital of Fudan University.Thirty-nine patients were included in this study.Their average age was 16.87±2.2 years when they came to our hospital.Totally,51% of the patients had isolated congenital vaginal atresia with a normal cervix,whereas the others had either cervical atresia or imperforate hymen.The primary presenting signs and symptoms included primary amenorrhea (71.8%),periodic abdominalgia (41.0%),abdominal pain (36.0%),dyspareunia (10.3%),menstrual disorders (5.1%),and pelvic mass (5.1%).Ultrasound and magnetic resonance imaging (MRI) were effective inspection methods for the screening of urogenital tract-associated anomalies.Vaginoplasty mainly included simple vagina reconstruction with insertion of a mold (n=22) and split-thickness skin grafting (n=4).In 64% of surgical patients,normal menstrual bleeding was achieved.Four of the patients subsequently became pregnant and delivered at term.Primary amenorrhea,periodic abdominalgia and abdominal pain are the main reasons for the post pubertal patients to visit doctors.Surgical methods can successfully provide these patients an opportunity for subsequent conservative management,can result in normal menstrual bleeding,resolve cyclic pelvic pain,and provide some potential for fertility.
ABSTRACT
To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and 'universal' preventive HPV peptide vaccine based on L1 conserved BCEs.
Subject(s)
Capsid Proteins/chemistry , Epitope Mapping/methods , Immunoglobulin G/blood , Oncogene Proteins, Viral/chemistry , Papillomaviridae/metabolism , Papillomavirus E7 Proteins/chemistry , Animals , Binding Sites , Capsid Proteins/immunology , Epitopes, B-Lymphocyte/analysis , Humans , Mice , Models, Molecular , Oncogene Proteins, Viral/immunology , Papillomavirus E7 Proteins/immunology , Papillomavirus Vaccines/immunology , Protein Conformation , RabbitsABSTRACT
OBJECTIVE: To comparatively evaluate the hematological toxicity (HT) associated with 3 concurrent chemoradiotherapies that are routinely used to treat cervical cancer, including 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and RapidARC and to establish a new normal tissue complication probability model of bone marrow (BM) to predict HT in cervical cancer patients undergoing concurrent chemoradiotherapy. METHODS: Patients with cervical cancer (N = 100) who received concurrent cisplatin and whole-pelvic radiotherapy were enrolled in this study. Dosimetric parameters (including V10, V20, V30, and V40 and mean doses to the pelvic bone) and HT were analyzed. RESULTS: The V20, V30, and V40 and mean doses to the BM were lower in the IMRT and RapidARC groups than in the 3DCRT group, and the RapidARC group had higher V10 and V40 and mean values than the IMRT group. The V20, V30, and V40 and the mean dose to the pelvic bone were positively correlated with HT. Generalized linear normal tissue complication probability models of white blood cell (WBC) and absolute neutrophil cell (ANC) nadirs and BM V20 were established as follows: WBC nadir = 3.382 - 4.056 ⢠V20 + 0.295 ⢠baseline of WBC (adjusted R = 0.246, F = 15.847) and ANC nadir = 2.438 - 2.780 ⢠V20 + 0.233 ⢠baseline of ANC (adjusted R = 0.236, F = 16.282). CONCLUSIONS: This study suggests that IMRT results in milder hematological toxicity than either 3DCRT or RapidARC. Dosimetric parameters were associated with the incidence of HT in cervical cancer patients who received concurrent chemoradiotherapies.
Subject(s)
Bone Marrow/radiation effects , Chemoradiotherapy/adverse effects , Hematologic Diseases/etiology , Radiotherapy, Conformal/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Female , Follow-Up Studies , Hematologic Diseases/diagnosis , Humans , Middle Aged , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Uterine Cervical Neoplasms/pathologyABSTRACT
Objective: To prepare the 5% and 10% chlorosalicylicamideï¼quinoid-2', 5-dichloro-4'-nitrosalicylanilide from niclosamideï¼ sustained-release granules ï¼LDS-SRGï¼ and evaluate their molluscicidal effect. Methods: The 5% and 10% LDS-SRG were prepared with screened carriers, surfactants, adhesives, defoamers and lubricants. Their bulk density, water content, repose angle, critical relative humidity, thermal stability and release rate were determined. Spraying method was used to test the molluscicidal effect of LDS-SRG at 1.6 g/m2. Meanwhile, 50% wettable powder of niclosamide ethanolamine salt (WPN) was applied as the positive control at 1.0 g/m2, and dechlorinated water was used as the blank control. The mortality of snails was calculated on days 3, 7 and 14 after administration. Results: The 5% and 10% LDS-SRG were red brown in color, showed good fluidity, and had bulk density of 0.655 g/ml and 0.594 g/ml, moisture content of 1.15% and 1.28%, repose angle of 39.8° and 39.7°, and critical relative humidity of 64.98% and 61.63%, respectively. Moreover, both showed good thermal stability. The release curve was stable for both 5% and 10% LDS-SRG during day 1 to day 9, and faster release for 5% LDS-SRG than for 10% LDS-SRG. The burst release occurred on days 10 and 15, and the steady release occurred from days 14 and 20 for 5% and 10% LDS-SRG respectively. The snail mortality on day 7 after 5% LDS-SRG 1.6 g/m2 administration and on day 14 after 10% LDS-SRG 1.6 g/m2 administration was both higher than 95%, and higher than that of the 50% WPN 1.0 g/m2 control (P<0.05). Conclusion: The 5% and 10% LDS-SRG show sustained-release potential and satisfactory molluscicidal effect by spraying, reaching the evaluation standard for molluscicidal agents.
Subject(s)
Delayed-Action Preparations , Animals , Molluscacides , Niclosamide , Snails , WaterABSTRACT
Objective: To evaluate the molluscicidal effect of the chlorosalicylicamide sustained-release granules (LDS-SRG) on Oncomelania hupensis. Methods: Seven effective concentrations or dosages of LDS-SRG, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 mg/L ï¼for immersion testï¼ or g/m2ï¼for spraying testï¼, were prepared from the original 5% and 10% concentrations or dosages in the laboratory. In the immersion test, each concentration of LDS-SRG was incubated with 3 packs of snailsï¼30 snails in each packï¼, and each pack was taken for snail counting at 24, 48 and 72 h respectively. In the spraying test, each dosage of LDS-SRG was applied to 200 snails, and the snail mortality was calculated in 50 randmoly collected snails on days 3 and 7, and in the whole on day 14 after administration. In the field immersion test, LDS-SRG at concentrations of 0.4, 0.8 and 1.6 g/m3 was incubated with 6 packs of snails ï¼30 snails in each packï¼, and each 2 packs were taken at 24, 48, and 72 h to calculate the snail mortality. In the field spraying test, 0.8, 1.6 and 3.2 g/m2 LDS-SRG was sprayed in 3 snail-positive ditches ï¼ï½100 m2ï¼, and 10 boxes of snails were selected in each ditch on days 3, 7 and 14 to calculate the snail mortality. The 50% wettable powder of niclosamide ethanolamine salt ï¼WPNï¼ with effective concentrations or dosages of 1.0 mg/L ï¼or g/m2 and g/m3ï¼ was used as the positive control. Fresh water served as the blank control. Results: In the labratory immersion test using the original concentration of 5%, both 0.1-6.4 mg/L LDS-SRG for 72 h and 1.6-6.4 mg/L LDS-SRG for 48 h caused 100% mortality; and the concentration lethal to 50% ï¼LC50ï¼ at 24, 48 and 72 h was 0.70, 0.01 and 0.01 mg/L respectively. When using the original concentration of 10%, both 0.1-6.4 mg/L LDS-SRG for 72 h and 0.2-6.4 mg/L LDS-SRG for 48 h caused 100% mortality; and the LC50 at 24, 48 and 72 h was 0.15, 0.01 and 0.01 mg/L respectively. The labratory spraying test showed that 7-day administration of 1.6 and 6.4 g/m2 LDS-SRG as well as 14-day administration of 3.2 and 6.4 g/m2 LDS-SRG prepared from 5% dosage, resulted in a snail mortality>95%, with the LD50 on days 3, 7 and 14 being 0.06, 0.16, and 0.18 g/m2; 14-day administration of 1.6 g/m2 LDS-SRG as well as 7-day administration of 6.4 g/m2 LDS-SRG prepared from 10% dosage, resulted in a snail mortality>95%, with the LD50 on days 3, 7 and 14 being 3.29, 0.75, and 0.16 g/m2. The mortality by various dosages of LDS-SRG prepared from 5% dosage was significantly higher than that of the control group (P<0.05). In the field immersion test, the snail mortality by 1.6 g/m3 LDS-SRG prepared from 5% and 10% concentrations for 72 h was 96.43% and 98.21% respectively (P>0.05 versus the control group). In the field spraying test, the snail mortality by 3.2 g/m2 LDS-SRG prepared from 5% dosage for 3, 7 and 14 days was 93.99%, 91.18% and 86.48% respectively, and that from 10% dosage was 94.95%, 93.50% and 85.43%, all significantly higher than that of the control group ï¼82.83%, 72.38% and 48.38%ï¼ï¼P<0.05ï¼; the snail mortality by 0.8 g/m2 LDS-SRG prepared from 5% dosage for 14 daysï¼66.51%ï¼ and that by 1.6 g/m2 LDS-SRG prepared from 5% dosage for 3 daysï¼84.61%ï¼ were both significantly higher than that by 10% LDS-SRGï¼20.13% and 43.06%ï¼ ï¼P<0.05ï¼. Conclusion: The 5% and 10% LDS-SRG used separately in the immersion test and the spraying test both meet the requirements of the national standard of Efficacy Test Methods and Evaluation of Molluscicide for Pesticide Registration.
Subject(s)
Delayed-Action Preparations , Molluscacides , Animals , Fresh Water , Niclosamide , SnailsABSTRACT
The present study aimed to investigate the regulatory mechanism of the AmpC enzyme by analyzing the construction and function of AmpCR, AmpE and AmpG genes in the Dhahran (DHA)1 plasmid of Klebsiella pneumoniae (K. pneumoniae). The production of AmpC and extendedspectrum ßlactamase (ESBL) were determined following the cefoxitin (FOX) inducing test for AmpC, preliminary screening and confirmation tests for ESBL in 10 DHA1 plasmid AmpC enzymes of K. pneumoniae strains. AmpCR, AmpD, AmpE and AmpG sequences were analyzed by polymerase chain reaction. The pACYC184X plasmid analysis system was established and examined by regulating the pAmpC enzyme expression. The electrophoretic bands of AmpCR, AmpD, AmpE and AmpG were expressed. Numerous mutations in AmpC + AmpR (AmpCR) and in the intergenic region cistron of AmpCAmpR, AmpD, AmpE and AmpG were observed. The homology of AmpC and AmpR, in relation to the Morganella morganii strain, was 99%, which was determined by comparing the gene sequences of Kp1 with those of Kp17 AmpCR. The specific combination of AmpR and labeled probe demonstrated a band retarded phenomenon and established a spatial model of AmpR. All the enzyme production strains demonstrated Val93âAla in AmpG; six transmembrane domains were found in AmpE in all strains, with the exception of Kp1 and Kp4, which had only three transmembrane segments that were caused by mutation. The DHA1 plasmid AmpC enzymes encoded by plasmid are similar to the inducible chromosomal AmpC enzymes, which are also regulated by AmpD, AmpE, AmpR and AmpG.
Subject(s)
Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Klebsiella pneumoniae/genetics , Plasmids/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/chemistry , Drug Resistance, Neoplasm , Genes, Bacterial , Klebsiella pneumoniae/drug effects , Microbial Sensitivity Tests , Models, Molecular , Mutation , Phenotype , Promoter Regions, Genetic , Protein Conformation , Protein Interaction Domains and Motifs , Repressor Proteins/genetics , Sequence Analysis, DNA , beta-Lactamases/chemistryABSTRACT
OBJECTIVE: To evaluate the effects of a novel molluscicide, the salt quinoid-2', 5-dichloro-4'-nitrosalicylanilide from niclosamide (LDS), with 10% wettable powder, in main schistosomiasis epidemic areas of China, including Hunan, Jiangxi, Hubei, Anhui, Jiangsu, Sichuan, Yunnan and Zhejiang Province. METHODS: In the immersion test, 6 effective concentrations of 10% LDS were tested respectively: 0.1, 0.2, 0.4, 0.6, 0.8, 1.0 g/m3 in the field; at the same time, 50% wettable powder of niclosamide ethanolamine salt (WPN) with effective concentrations of 1.0 g/m was used as the molluscicide control, and the fresh water as the blank control, then the mortality rates of 0. hupensis snails were recorded at 24 h, 48 h and 72 h after the immersion. In the spraying test and powder-spraying test, 5 effective dosages of 10% LDS were tested respectively: 0.2, 0.4, 0.6, 0.8, 1.0 g/m2, while 50% WPN 1.0 g/m2 was used as the molluscicide control, and the fresh water as the blank control in the field for 1 d, 3 d and 7 d, then the mortality rates of O. hupensis snails were recorded at 1 d, 3 d and 7 d after the spraying and powder-spraying. RESULTS: The snail mortality rates of LDS using the immersion test for 72 h were more than 95% in the field of eight provinces (0.1 g/m in Sichuan, Jiangxi, Jiangsu and Zhejiang provinces, 0.2 g/m3 in Yunnan, Hunan and Hubei provinces, and 0.4 g/min Anhui Province); the snail mortality rates of LDS using the spraying test for 7 d were more than 85% (0.2 g/m2 in Hunan, Hubei, Jiangxi and Zhejiang provinces, 0.4 g/m2 in Sichuan and Anhui provinces, 0.6 g/m2 in Yunnan and Jiangsu provinces). The snail mortality rates of LDS the powder-spraying test for 7 d were more than 85% (0.6 g/m2 in Yunnan, Sichuan, Hubei, Jiangxi, Anhui, Jiangsu and Zhejiang provinces). According to the standards of "Efficacy test methods and evaluation of molluscicide for pesticide registration (NY/T 1617-2008)", LDS is a qualified molluscicide. CONCLUSIONS: LDS has good molluscicidal effects through the immersion, spraying and powder-spraying test in the fields. It is suitable for a variety of environments to control O. hupensis snails of schistosomiasis endemic areas in China. The recommended dosages of LDS are 0.1-0.2 g/m3 by the immersion method, 0.2-0.4 g/m2 by the spraying method, and 0.4-0.6 g/m2 by the powder-spraying method in the fields.
Subject(s)
Molluscacides/pharmacology , Schistosomiasis/prevention & control , Snails , Animals , China/epidemiology , Schistosomiasis/epidemiology , Schistosomiasis/transmissionABSTRACT
OBJECTIVE: To study the changes of cerebral function and pathological morphology before and after the antiparasitic treatment with albendazole and praziquantel in patients with cerebral cysticercosis. METHODS: The data of EEG and neuroimaging of 412 patients with cerebral cysticercosis were retrospectively analyzed. RESULTS: Before the treatment, the mild abnormality, moderate abnormality, and severe abnormality were observed in 40.53%, 45.63% and 13.84% of the patients respectively, which mainly showed the diffuse or focal irregular slow waves, or epileptiform discharges found in the abnormal brain waves. CT/MRI manifestation could be divided into six types, including single sacculus type (23.59%), multiple sacculus type (44.42%), encephalitis type (13.59%), coexistence of macrocyst and sacculus type (4.85%), calcification type (2.18%), and mixed type (11.41%). After 3 courses of the treatment, the normal and improved EEGs were observed in 79.85% and 20.15%, respectively. CT/MRI showed the foci being all absorbed (77.18%), being most absorbed (20.63%), and being no changes (20.18%) which were calcified focus. When cerebral cysticercosis were in acute stage (the single and multiple sacculus type, encephalitis type, and macrocyst and sacculus coexistence type), the therapeutic effect was good; while in the mixed type, the therapeutic effect was relatively poor. If cysticercosis were in the calcification stage, the patients only needed the heteropathy. CONCLUSIONS: In the patients with cerebral cysticercosis, EEGs show the mild to severe abnormalities, and CT/MRI mainly shows the multiple sacculus type. After the treatment, the abnormal EEGs are gradually recovered and the low density foci can be all absorbed, but some calcified focus still exist in some patients.
Subject(s)
Antiparasitic Agents/therapeutic use , Electroencephalography , Neurocysticercosis/diagnosis , Neurocysticercosis/drug therapy , Neuroimaging , Adolescent , Adult , Aged , Albendazole/therapeutic use , Female , Humans , Male , Middle Aged , Neurocysticercosis/diagnostic imaging , Praziquantel/therapeutic use , Tomography, X-Ray Computed , Young AdultABSTRACT
This paper reports the diagnosis and therapy of one case of Dipylidium caninum infection in an infant.
Subject(s)
Cestoda/physiology , Cestode Infections/diagnosis , Cestode Infections/drug therapy , Animals , Cestode Infections/transmission , Humans , Infant , MaleABSTRACT
This study aimed to explore Semaphrin4D (Sema4D) expression and clinical significance in non-small cell lung cancer (NSCLC), and to define the roles and mechanisms of Sema4D in regulating the malignant behaviors of A549 cells by small interfering RNA (siRNA). Firstly, immunohistochemistry revealed that Sema4D was more frequently expressed in NSCLC than in lung benign lesion (P<0.05) and its overexpression was associated with low differentiation (P<0.05), poor pTNM staging (P<0.05) and occurrence of lymph node (LN) metastasis (P<0.05). Endogenous Sema4D expression was suppressed by Sema4D siRNA in A549 cells overexpressing Sema4D. Protein levels of Sema4D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation (P<0.05), migration (P<0.05) and invasion (P<0.05) in A549 cells. These findings suggest that Sema4D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4D may be a useful approach for the treatment of NSCLC.
Subject(s)
Antigens, CD/biosynthesis , Carcinoma, Non-Small-Cell Lung , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Semaphorins/biosynthesis , Aged , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Disease-Free Survival , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Survival RateABSTRACT
The emission characteristics of five typical crops, including wheat straw, rice straw, oil rape straw, soybean straw and fuel wood, were investigated to explore the gas and particulates emission of typical biomass burning in Yangzi-River-Delta area. The straws were tested both by burning in stove and by burning in the farm with a self-developed measurement system as open burning sources. Both gas and fine particle pollutants were measured in this study as well as the chemical composition of fine particles. The results showed that the average emission factors of CO, NO, and PM2,5 in open farm burning were 28.7 g.kg -1, 1.2 g.kg-1 and 2.65 g kg-1 , respectively. Due to insufficient burning in the low oxygen level environment, the emission factors of stove burning were higher than those of open farm burning, which were 81.9 g kg-1, 2. 1 g.kg -1 and 8.5 gkg -1 , respectively. Oil rape straw had the highest emission factors in all tested straws samples. Carbonaceous matter, including organic carbon(OC) and element carbon(EC) , was the foremost component of PM2, 5from biomass burning. The average mass fractions of OC and EC were (38.92 +/- 13.93)% and (5.66 +/-1.54)% by open farm burning and (26.37 +/- 10. 14)% and (18.97 +/- 10.76)% by stove burning. Water soluble ions such as Cl-and K+ had a large contribution. The average mass fractions of CI- and K+ were (13.27 +/-6. 82)% and (12.41 +/- 3.02)% by open farm burning, and were (16.25 +/- 9.34)% and (13.62 +/- 7.91)% by stove burning. The K +/OC values of particles from wheat straw, rice straw, oil rape straw and soybean straw by open farm burning were 0. 30, 0. 52, 0. 49 and 0. 15, respectively, which can be used to evaluate the influence on the regional air quality in YRD area from biomass burning and provide direct evidence for source apportionment.