IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation.

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer (NSCLC). Although researchers have disclosed that interleukin 17 (IL-17) can increase matrix metalloproteinases (MMPs) induction causing NSCLC cell metastasis, the underlying mechanism remains unclear. In the study, we found that IL-17 receptor A (IL-17RA), p300, p-STAT3, Ack-STAT3, and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17. p300, STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3, Ack-STAT3 and MMP19 level as well as the cell migration and invasion. Mechanism investigation revealed that STAT3 and p300 bound to the same region (-544 to -389 nt) of MMP19 promoter, and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity, p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17. Meanwhile, p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact, synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion. Besides, the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300, STAT3 or MMP19 gene plus IL-17 treatment, the nodule number, and MMP19, Ack-STAT3, or p-STAT3 production in the lung metastatic nodules were all alleviated. Collectively, these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation, which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

[Comparison of safety of total laparoscopic versus laparoscopic-assisted radical gastrectomy for distal gastric cancer in older patients].

Objective: To compare the effectiveness of total laparoscopic versus laparoscopic-assisted distal gastrectomy and investigate the safety and replicability of total laparoscopic distal gastrectomy in older patients. Methods: This was a retrospective cohort study. The inclusion criteria were as follows: (1) age ≥65 years; (2) malignant gastric tumor diagnosed pathologically preoperatively; (3) Eastern Cooperative Oncology Group performance status score 0-1; (4) Grade I-III American Society of Anesthesiologists physical status; (5) preoperative clinical tumor stage I-III; (6) total laparoscopic or laparoscopic-assisted distal gastrectomy performed; and (7) gastrointestinal tract reconstruction using uncut Roux-en-Y or Billroth-II+Braun procedure. Patients who had received neoadjuvant therapy, undergone conversion to open surgery, or had serious comorbidities or incomplete data were excluded. The clinical data of 129 patients who met the above criteria and had undergone laparoscopic surgery for gastric cancer from January 2012 to December 2021 in the Gastrointestinal Cancer Center in the Beijing Cancer Hospital were analyzed. According to the operation method, the patients were divided into total laparoscopic group and laparoscopic-assisted group. Variables studied comprised: (1) surgical procedure and postoperative recovery; (2) postoperative pathological findings; and (3) postoperative complications. Measurement data with skewed distribution are represented as mean(quartile 1, quartile 3). Comparisons between groups were evaluated using the Mann-Whitney U test. Results: After propensity score matching in a 1:1 ratio, there were 40 patients in the total laparoscopic distal gastrectomy group and 40 in the laparoscopic-assisted distal gastrectomy group. Baseline characteristics did not differ significantly between the two groups (all P>0.05).Compared with the laparoscopic-assisted group, the total laparoscopic group had shorter main incisions (4.1±1.0 cm vs. 8.5±2.8 cm, t=9.375, P<0.001), time to fluid intake [4.0 (3.0, 4.8) days vs. 5.0 (4.0, 6.0) days, Z=2.167, P=0.030], and duration of indwelling abdominal drainage catheter [6.0 (6.0, 7.0) days vs. 7.0 (6.0, 8.0) days, Z=2.323, P=0.020]. Numerical Rating Scale scores on postoperative days 1 and 2 were higher in the total laparoscopic than the laparoscopic-assisted group [2.5 (1.0, 3.0) vs. 1.5 (1.0, 2.0), Z=1.980, P=0.048; 2.0 (1.0, 3.0) vs. 1.0 (1.0, 2.0), Z=2.334, P=0.020, respectively]. However, there were no significant differences between the groups in operation time, intraoperative blood loss, white blood cell count, hemoglobin concentration, or albumin concentration on postoperative day 1, time to ambulation, mean time to bowel movement, postoperative admission to the intensive care unit, length of postoperative hospital stay, or Numerical Rating Scale scores on postoperative day 3 (all P>0.05). There were also no significant differences between the two groups in maximum tumor diameter, pathological tumor type, total number of lymph nodes dissected, or total number of positive lymph nodes (all P>0.05). The incidence of postoperative complications was 15.0% (6/40) in the total laparoscopic group and the laparoscopic-assisted group; these differences are not significant (χ2<0.001, P>0.999). Conclusions: Compared with laparoscopic-assisted radical gastrectomy for distal gastric cancer, total laparoscopic surgery has the advantages of shorter incision, shorter time to fluid intake, and shorter duration of indwelling abdominal drainage catheter in older patients (age ≥65 years). Total laparoscopic radical gastrectomy for distal gastric cancer does not increase the risk of postoperative complications and could therefore be performed more frequently.

MRI characteristics for differentiating mucinous borderline ovarian tumours from mucinous ovarian cancers.

AIM: To investigate the magnetic resonance imaging (MRI) characteristics that could differentiate mucinous borderline ovarian tumours (MBOTs) from mucinous ovarian cancers (MOCs). MATERIALS AND METHODS: MRI data from 75 patients with MBOTs and 38 patients with MOCs were reviewed retrospectively. The clinicopathological and MRI features, including age, bilaterality, maximum diameter (MD), shape, margin, configuration, cystic-solid interface, papillae, MD of the cyst walls and septa, MD of the solid components, number of cysts, honeycomb loculi, signal of the cystic and solid components, apparent diffusion coefficient (ADC) value and enhancement ratio of the solid components, peritoneal implants and ascites, were compared using univariable analysis and multivariable logistic regression analysis. RESULTS: There were 76 MBOTs and 39 MOCs, and median patient age was 41 years (range 16-77 years) and 51 years (range 15-90 years), respectively (p=0.004). There were significant differences between MBOTs and MOCs regarding the presence of papillae (p=0.013), MD of the solid components (p=0.001), enhancement ratio of the solid components (p=0.003), ADC value (p<0.001), and ascites (p<0.001). The optimal cut-off ADC value was 1.16 × 10-3 mm2/s, with a sensitivity of 87.1%, a specificity of 83.3%, and an area under the curve (AUC) of 0.917. CONCLUSION: Compared with MOCs, MBOTs had fewer papillae or solid components, lower enhancement ratio, higher ADC values, and were less likely to have moderate or massive ascites.

Invasive Bacterial Diseases in Northern Canada, 2006-2013.

BACKGROUND: Northern populations were at a high risk of developing invasive bacterial diseases (IBDs). Since the last published study that described IBDs in Northern Canada, a number of vaccines against some bacterial pathogens have been introduced into the routine childhood immunization schedule. OBJECTIVE: To describe the epidemiology of IBDs in Northern Canada from 2006 to 2013. METHODS: Data for 5 IBDs (invasive pneumococcal disease (IPD), invasive Haemophilus influenzae disease (Hi), invasive Group A streptococcal disease (iGAS), invasive meningococcal disease (IMD) and invasive Group B streptococcal disease (GBS)) were extracted from the International Circumpolar Surveillance (ICS) program and the Canadian Notifiable Diseases Surveillance System. Incidence rates were calculated per 100,000 population per year. RESULTS: During the study period, the incidence rates of IPD ranged from 16.84-30.97, iGAS 2.70-17.06, Hi serotype b 0-2.78, Hi non-b type 2.73-8.53, and IMD 0-3.47. Except for IMD and GBS, the age-standardized incidence rates of other diseases in Northern Canada were 2.6-10 times higher than in the rest of Canada. Over the study period, rates decreased for IPD (p=0.04), and iGAS (p=0.01), and increased for Hi type a (Hia) (p=0.004). Among IPD cases, the proportion of pneumococcal conjugate vaccine (PCV)7 serotypes decreased (p=0.0004) over the study period. Among Hi cases, 69.8% were Hia and 71.6% of these were in children under than 5 years. Of 13 IMD cases, 8 were serogroup B and 2 of them died. CONCLUSION: Northern population in Canada, especially infants and seniors among First Nations and Inuit, are at a high risk of IPD, Hi and iGAS. Hia is the predominant serotype in Northern Canada.

Evaluation of the Enhanced Invasive Pneumococcal Disease Surveillance System (eIPDSS) Pilot Project.

BACKGROUND: Invasive pneumococcal disease (IPD) causes significant morbidity in Canada, yet even with routine surveillance, it is difficult to interpret current IPD trends in serotype distribution and antimicrobial resistance. The enhanced Invasive Pneumococcal Disease Surveillance System (eIPDSS) pilot project was designed to facilitate a better understanding of IPD trends at the national level by linking epidemiologic and laboratory (epi-lab) data. OBJECTIVES: To evaluate the eIPDSS by assessing five attributes (usefulness, data quality, simplicity, acceptability and timeliness) and to develop recommendations for future national IPD surveillance. METHODS: An evaluation was developed that assessed the five key attributes through a qualitative survey sent to eight eIPDSS users as well as a quantitative analysis of the eIPDSS database. Recommendations were based on the results of both the survey and the analysis. RESULTS: The response rate to the survey was 100%. The majority of the survey respondents found the eIPDSS to be useful (75%), simple (100%) and acceptable (86%). Analysis of the eIPDSS database revealed that the majority of IPD cases (61%) were assessed as timely. Data quality and data management mechanisms were identified as issues by both survey respondents and the analysis of the database. Consultation with public health, regular audits and upgrades to the platform are recommended to address data quality and management issues. CONCLUSION: The epi-lab linked data of the eIPDSS enables the detection and analysis of IPD serotype distribution and antimicrobial resistance trends. This web-based system facilitates data collection and is simple, acceptable and timely. With improvements that address data quality and management issues, it is feasible to develop a national surveillance system that links epi-lab data.

Monitoring invasive bacterial diseases in the North American Arctic via the International Circumpolar Surveillance Project.

This paper summarizes the most recent Invasive Bacterial Diseases (IBD) Working Group meeting of the International Circumpolar Surveillance (ICS) project. The ICS is a population-based surveillance network for invasive bacterial diseases that provides a mechanism to determine changes in incidence rates and antimicrobial resistance. The meeting took place in Montreal, Canada on February 12-13, 2014. Data were included from participating Canadian provincial and territorial jurisdictions as well as from the State of Alaska. This report is based on the audio records of the meeting as well as the meeting presentations. The ICS IBD Working Group focuses on invasive diseases caused by: Streptococcus pneumoniae (Sp), Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), Group A Streptococcus (GAS) and Group B Streptococcus (GBS). Data on invasive disease caused by each of these organisms were reviewed through December 2012-2013. Although the incidence of some of these vaccine-preventable invasive diseases has decreased, emergence of H. influenzae serotype a (Hia) in both Alaska and Northern Canada was noted. An interlaboratory quality control (QC) program is ongoing to monitor laboratory proficiencies for serotyping.

Enhanced surveillance of invasive meningococcal disease in Canada, 2006-2011.

OBJECTIVE: The purpose of this report is to describe the epidemiology of invasive meningococcal disease (IMD) in Canada from 2006 to 2011. METHODS: Data from the Enhanced Invasive Meningococcal Disease Surveillance System and national population estimates were selected for descriptive and inferential analyses. The geographic, demographic, seasonal and subtype distributions as well as clinical characteristics of the IMD cases were examined. Incidence and mortality rates were calculated per 100,000 population per year; 95% confidence intervals (CI) were calculated for rate comparison. The direct method was used for age standardization. Proportions were compared using the chi-squared test at a p<0.05 significance level. RESULTS: During the study period, the mean incidence rates of IMD were 0.58 (total), 0.33 (serogroup B), 0.07 (serogroup C), 0.03 (serogroup W-135) and 0.10 (serogroup Y). The median age for serogroups B, C, W-135 and Y was 16, 43, 38 and 47 years respectively. The mean age-specific incidence rates among infants under 1 year of age (7.35, CI: 5.38-9.32) and children from 1 to 4 years of age (1.89, CI: 1.54-2.24) were significantly higher than those in any other age group. The mean case fatality ratio was 8.1% (range 4.3%-14.3%). The average number of cases that occurred per month was significantly higher (p<0.0001) in winter (18 cases) than in summer (12 cases). CONCLUSION: IMD is still endemic in Canada. Although individuals at any age can be affected, infants under 1 year of age are at the greatest risk, followed by children aged 1-4 years and individuals aged 15-19 years. Following the implementation of routine childhood immunization programs with monovalent meningococcal C conjugate vaccines (MenC) in all provinces and territories (beginning in 2007), the incidence of serogroup C has decreased significantly over the study period and is now at an all-time low. Serogroup B is the leading cause of IMD, and diseases of serogroup W-135 and Y have stabilized at relatively lower incidence rates. With the addition of immunization programs using quadrivalent conjugate meningococcal vaccines (MCV4), we would expect further reductions in the incidence of meningococcal infection in Canada.

Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer.

OBJECTIVE: Carcinoembryonic antigen (CEA) in the serum and the tumour tissue of colorectal cancer (CRC) patients is the most commonly used tumour marker for the diagnosis and evaluation of prognosis or recurrence after treatment, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumour tissue in CRC. METHOD: A total of 173 patients with CRC in stages I-III were retrospectively assessed with the endpoint of recurrence or metastasis after curative operation. CEA was assessed both in serum and tumour tissue. RESULTS: 37.0% (64/173) patients had a high level of CEA in serum (S-CEA) while 39.3% (68/173) had high CEA in tumour tissue (T-CEA). There were no significant differences in clinico-pathological features between the low and high S-CEA or T-CEA groups. The high S-CEA group had a worse prognosis than the low S-CEA group but the difference was not significant. The high T-CEA group had a significantly poorer prognosis than the low T-CEA group (P = 0.028) in the univariate analysis. The multivariate analysis demonstrated that the T-CEA was an independent prognosis factor in CRC. Because many factors would affect the concentration of S-CEA, there was no correlation between S-CEA and T-CEA directly. CONCLUSION: Our study suggests that a high T-CEA concentration may be a useful and independent predictor for poor outcome after surgery in CRC patients. It may be stronger than a high preoperative serum CEA level.

[Effects of cadmium chloride on the malignant transformation of human embryo lung fibroblasts].

The malignant transformation of human embryo lung fibroblast (HELF) induced by CdCl2 was tested by 3H-TdR incorporation, chromosome analysis and flow cytometry. Chromosome aberration, the ratio of cells in different cell cycle phases and the quantities of DNA synthesis of different groups were determined. The results showed that the morphology of HELF changed in three levels of cadmium chloride (I 0.004 mumol/L, II 0.02 mumol/L and III 0.04 mumol/L) treated for three times. The cell growth was disordered and overlapping without density regulating effect and the transforming foci were formed. The quantities of chromosome were decreased or increased and the dicentric and acentric fragments were found in experimental groups. The ratio of cells in S phase increased and the quantities of DNA synthesis in experimental groups were 2.4-3.8 times higher than that of negative control group. The chromosome aberration of cells, the increase of cells in S phase and the increase of DNA synthesis may play some roles in the malignant transformation of HELF induced by CdCl2.

Cloning and expression of propionyl acylase gene of Streptomyces mycarofaciens mutant.

The midecamycin producer, S. mycarofaciens mutant, which has propionyl acylase activity, can convert spiramycin into propionyl spiramycin. Plasmid pIJ702 was used as a vector for the cloning of propionyl acylase gene. After shot-gun cloning, the DNA fragments of the mutant were cloned in S. lividans TK54. The results of TLC and HPLC showed that No.9 transformant can convert spiramycin into propionyl spiramycin. It demonstrated that the propionyl acylase gene was cloned and expressed in S. lividans TK54. The insert fragment of No.9 recombinant plasmid is about 4.16 kb. Southern hybridization showed that the fragment originated from S. mycarofaciens mutant. The restriction endonuclease map of No.9 recombinant plasmid was constructed.

Doppler echocardiographic evaluation of pulmonary artery pressure in pneumonia of infants and children.

Previously, there was insufficient evidence to confirm that pneumonia in infants and children might lead to the development of pulmonary hypertension. Recently, it has been shown that acceleration time corrected for heart rate (ATc) and the ratios of right ventricular preejection period to right ventricular ejection time (RPEP/RVET) and of right ventricular preejection period to acceleration time (RPEP/AT) derived from Doppler echocardiography correlated well with pulmonary artery pressure (PAP). To approach PAP in patients with infantile pneumonia, we measured RPEP/RVET, RPEP/AT, and ATc in 105 infants and children with pneumonia and in 17 controls, using a commercially available 2-dimensional echocardiograph (Toshiba SSH-40A) with SDS-21B Doppler unit. An increase of varying degrees in both ratios and ATc was noted during acute illness and significant differences in ratios RPEP/RVET and RPEP/AT were found among patients with mild, moderate, and severe disease. This suggested that PAP increased to different extents in the acute stage of illness and that the degree of increase was related to the severity of disease.

Pulmonary artery pressure evaluated by pulsed Doppler echocardiography in children with a left-to-right intracardiac shunt.

In a study of 25 children with left-to-right intracardiac shunt we found a good correlation (r greater than 0.92; p less than 0.001) between right ventricular pre-ejection period/acceleration time, derived from pulsed Doppler echocardiography, and pulmonary artery systolic, diastolic, and mean pressures, measured at cardiac catheterization. This may enhance the noninvasive estimation of pulmonary artery pressure.

[Molecular cloning of butirosin biosynthesis genes. I. Construction and characterization of recombinant plasmid DNA No. 2 and No. 11].

B. circulans NRRL-B 3312 is a butirosin-producing strain, butirosin being one of aminoglycoside antibiotics. We used shotgun strategy for molecular cloning of butirosin biosynthesis genes. EcoRI digests of B. circulans NRRL-B 3312 chromosome DNA were ligated to EcoRI digests of plasmid pUB110 with T4-DNA ligase. Recombinant DNA was transformed into competent cells of B. subtilis 168. Kanr transformants were selected on medium containing kanamycin (5 micrograms/ml). Results showed that kanamycin and neomycin resistance levels were higher than that of pUB110 for both No. 2 and No. 11 recombinant plasmid DNA. Restriction enzyme maps were constructed for two recombinant plasmid DNA No. 2 and No. 11 respectively. Southern hybridization showed that there were some homogenous DNA sequences between No. 2 and No. 11 recombinant plasmid DNA and B. circulans NRRL-B 3312 DNA.

Electron microscopy of DNA molecules from blastoderm nuclei and yolk granules beneath blastoderm of fertilized and unincubated chicken eggs.

The DNA molecules isolated from the blastoderm nuclei and yolk granules beneath the blastoderm of fertilized and unincubated chicken eggs were observed under electron microscope, using the DNA sample of calf thymus as control. The results showed that both nuclear and yolk DNAs are linear, and their molecules are very similar to those of thymus DNA in shape. Since chromatin was first prepared from blastoderm nuclei and yolk granules respectively and then DNA was isolated from both of chromatin samples, it could be concluded that yolk granules possess both DNA chromatin as nuclei do.

Chromatin and DNA of yolk granules beneath "blastoderm region" of unfertilized chicken egg.

Electron microscopic study shows that the chromatin structure of yolk granules beneath the "blastoderm region" of the unfertilized chicken egg is identical to that of yolk granules beneath the blastoderm of the fertilized and unincubated chicken egg, and both chromatin structures are very similar to those of blastoderm nuclei. Furthermore the molecular shapes of DNA of both yolk granules are also very similar to those of the blastoderm nuclei, being all linear. Based on these observations, we have come to the conclusion that chromatin and DNA widely exist in the yolk when yolk granules have reached their development-specified competence. The results indicate further that the yolk granules are capable of synthesizing DNA, and provide the condition for the interaction of DNA with histones to form chromatin through self-organization.

Electron microscopic studies on the chromatin of blastoderm nuclei and yolk granules beneath blastoderm of fertilized and unincubated chicken eggs.

Chromatin prepared both from the yolk granules beneath the blastoderm and from the nuclei of the blastoderm cells of fertilized and unincubated chicken eggs was examined under electron microscope and its structure was compared. The results indicate that the above two kinds of chromatin fibers seem to have no apparent difference in structural relation and diameter. The electron microscopic appearances of the basic structures of both kinds of chromatin are all "beads-on-a-string"-shaped filaments. After the digestion of chromatin from both raw materials with DNase I, the connecting strings of chromatin fibers were cut off, only the scattered beads could be observed under electron microscope. The diameter of the scattered beads is equal to that of the beads on the chromatin fibers, and most of them are 150 A in diameter.