Assessing Obstetric Anal Sphincter Injuries: A Comparison of Exoanal and Endoanal Ultrasound.

OBJECTIVES: To explore the differences in assessing obstetric anal sphincter injuries (OASI) between transperineal ultrasound (TPUS) and endoanal ultrasound (EAUS) and test relationships between ultrasound findings and anal incontinence (AI) symptoms. METHODS: A group of 196 women with a history of vaginal delivery was recruited. OASI was detected in a set of 5 slices by EAUS and 8 slices by TPUS. OASI grading was performed on TPUS rules and EAUS rules. A "significant sphincter defect" was diagnosed by TPUS and EAUS using "2/3 rules." Symptoms of AI were determined using the St Mark's Incontinence Score (SMIS). Ultrasound findings were compared between the two methods and correlated with symptoms. RESULTS: Of 196 women, 29 (14.8%) suffered from AI with a mean SMIS of 12.1 ± 4.5, and 70 (35.7%) women with a mean age of 57 years had suspected OASI on imaging. Twenty-one (10.7%) "significant defects" were diagnosed by TPUS and 24 (12.2%) by EAUS. OASI Grades on TPUS had good agreement with EAUS rules (k = 0.70, P < .001). Logistic regression analysis showed that OASI Grade on imaging and "significant sphincter defects" seen on both forms of imaging were associated with AI symptoms. The odds ratio was 46 and 38 for "significant defects" on TPUS and EAUS, and 14 and 7 for OASI 3b+ on TPUS and EAUS in predicting AI, respectively. CONCLUSIONS: "Significant defects" diagnosed by EAUS or TPUS and OASI Grade 3b+ predict AI symptoms. The diagnostic performance of endoanal and exoanal ultrasound (EAUS and TPUS) appear to be very similar.

Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways.

BACKGROUND: Mesangial proliferative glomerulonephritis (MsPGN) accounts for a main cause of chronic kidney disease (CKD), chronic renal failure and uremia. This paper aimed to examine the effect of Ntrk1 on MsPGN development, so as to identify a novel therapeutic target for MsPGN. METHODS: The MsPGN rat model was constructed by single injection of Thy1.1 monoclonal antibody via the tail vein. Additionally, the Ntrk1 knockdown rat model was established by injection of Ntrk1-RNAi lentivirus via the tail vein. Periodic acid-schiff staining and immunohistochemistry (IHC) were performed on kidney tissues. Moreover, the rat urinary protein was detected. Mesangial cells were transfected and treated with p38 inhibitor (SB202190) and ERK inhibitor (PD98059). Meanwhile, the viability and proliferation of mesangial cells were analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine assays. Gene expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot (WB) assays. RESULTS: The proliferation of mesangial cells was enhanced in glomerulus and Ki67 expression was up-regulated in renal tubule of MsPGN rats. The urine protein level increased in MsPGN rats. Pro-inflammatory factors and Ntrk1 expression were up-regulated in glomerulus of MsPGN rats. Ntrk1 up-regulation promoted the viability, proliferation, expression of pro-inflammatory factors and activation of the STAT3, p38 and ERK signaling pathways in mesangial cells. Ntrk1 knockdown reduced mesangial cell proliferation, urine protein, pro-inflammatory factors, activation of STAT3, p38 and ERK signaling pathways in glomerulus, and decreased Ki67 expression in renal tubule of MsPGN rats. Treatment with SB202190 and PD98059 reversed the effect of Ntrk1 on promoting the viability, proliferation and inflammatory response of mesangial cells. CONCLUSION: Ntrk1 promoted mesangial cell proliferation and inflammation in MsPGN rats by activating the STAT3 and p38/ERK MAPK signaling pathways.

Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis.

Hypoxia is a typical microenvironment feature in almost all solid tumors and is frequently associated with growth of cancers including colorectal cancer (CRC). This study focuses on the influence of hypoxic microenvironment on the activity of CRC cells and the molecules involved. CRC cells were cultured under hypoxic conditions for 48 h, after which the proliferation, migration, invasion, and epithelial-mesenchymal transition activities of cells were increased. MicroRNA- (miR-) 19a was significantly upregulated in cells after hypoxia exposure according to a microarray analysis. STAT3 was confirmed as an upstream regulator of miR-19a which bound to the promoter region of miR-19a at the 96 bp/78 bp sites, and miR-19a bound to the PTEN mRNA to activate the PI3K/AKT signaling pathway. Hypoxia exposure induced STAT3 phosphorylation and PTEN knockdown in CRC cells. Silencing of STAT3 reduced the hypoxia-induced activity of CRC cells, whereas the malignant behaviors of cells were restored after miR-19a upregulation but blocked after PTEN overexpression. Similar results were reproduced in vivo where downregulation of STAT3 or overexpression of PTEN suppressed tumor growth and metastasis in nude mice. This study demonstrated that hypoxia augments activity and malignant behaviors of colorectal cancer cells through the STAT3/miR-19a/PTEN/PI3K/AKT axis.

Effect of individualized diabetes education for type 2 diabetes mellitus: a single-center randomized clinical trial.

BACKGROUND: To evaluate the effect of individualized education for patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 280 patients (158 males, mean age 63 ± 10 years) with T2DM were randomly divided into study and control group. Eysenck Personality questionnaire was used to assess the personality of the patients in the study group, which was provided us one-on-one counseling and individualized management plan. Group education was provided to the control group. RESULTS: At the end of the study, the body mass index (21.5±2.5 vs 23.6±1.6 kg/m2, P =0.002), waist circumference (83.7±6.4 vs 85.7±7.7 cm, P =0.03), fasting blood glucose (6.0±0.8 vs 6.9±2.1 mmol/L, P =0.004), HbA1c (6.2±0.6% vs 6.9±3.1%, P =0.03), systolic blood pressure (130.1±8.8 vs 135.1±8.4 mmHg, P =0.003),triglyceride (1.21±0.66 vs 1.46±0.58 mmol/L) and low-density lipoprotein (2.36±0.44 vs 2.84±0.64 mmol/L, P =0.03) in the study group was lower than in the control group. CONCLUSION: Individualized diabetes education is more effective than group education in facilitating the control of type 2 diabetes.

[Comparison of anorectal pressure after procedure for prolapse and hemorrhoids versus Doppler-guided hemorrhoidal artery ligation for grade III hemorrhoids].

OBJECTIVE: To compare the long-term anorectal manometry of patients with grade III hemorrhoids treated by procedure for prolapse and hemorrhoids (PPH) or Doppler-guided hemorrhoidal artery ligation (DGHAL). METHODS: A total of 114 patients with grade III hemorrhoids in our department in 2010 were prospectively enrolled, and divided into PPH group (63 cases) and DGHAL group (51 cases) according to patient preference. Patients received anorectal pressure examination 2, 6, 12, 18 months after operation, including rectal resting pressure, anal resting pressure, maximal anal contractive pressure and length of high-pressure band. Anorectal manometries between two procedure groups were compared. RESULTS: In every time point of follow-up, as compared to PPH group, DGHAL group presented higher anal resting pressure[postoperative 2 months: (56.2±2.6) mmHg vs. (43.2±3.1) mmHg, postoperative 6 months: (55.2±2.1) mmHg vs. (45.1±2.5) mmHg, postoperative 12 months: (53.2±3.0) mmHg vs. (40.2±3.2) mmHg, postoperative 18 months: (55.3±2.6) mmHg vs. (43.2±2.5) mmHg, all P<0.01], and longer length of high-pressure band [postoperative 2 months: (3.45±0.14) cm vs. (2.95±0.22) cm, postoperative 6 months: (3.46±0.12) cm vs. (2.94±0.26) cm, postoperative 12 months: (3.45±0.12) cm vs. (3.01±0.21) cm, postoperative 18 months: (3.56±0.12) cm vs. (3.02±0.23) cm, all P<0.01]. While no significant differences of maximal anal contractive pressure and rectal resting pressure were found between the two groups. CONCLUSION: Both PPH and DGHAL are safe procedures and have similar efficacy in the treatment of grade III hemorrhoids, while DGHALpossesses better efficacy in the time of anal function recovery and the maintenance of anal function.

Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case-control study.

The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P = 0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95 % CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR = 2.75, 95 % CI: 1.14-6.60) and in young subjects (OR = 2.05, 95 % CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC.

Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population.

BACKGROUND: Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003-2004 among CAP of adult Chinese urban populations. METHODS: Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed. RESULTS: Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with beta-lactam antibiotics alone and with combination of a beta-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a beta-lactam plus a macrolide, or a fluoroquinolone) than with beta-lactam alone (75.8% vs. 42.9%, p = 0.045). CONCLUSION: In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

[The action of active efflux system on multi-drug resistance in methicillin resistant Staphylococcus aureus].

OBJECTIVE: To study the active efflux gene qacB, qacJ and smr in methicillin resistant Staphylococcus aureus (MRSA) and to investigate their effect on the multi-drug resistance (MDR) of MRSA. METHODS: The three pairs of ideal primers of active efflux gene qacB, qacJ and smr were designed by computer with Primer Premier 5.0 software. A total of 124 clinical isolates of MRSA were amplified respectively by polymerase chain reaction (PCR) with above mentioned primers. The PCR products were separated by electrophoresis on an 1.5% agarose gel with 0.5 microg/ml ethidium bromide. Reserpine inhibition test was used to observe the changes of the susceptibility to antibiotics of MRSA which had qacB, qacJ and smr genes separately. RESULTS: Of the 124 strains of MRSA, 86 strains had qacB, 45 strains had qacJ and 32 strains had smr gene. Reserpine inhibition test showed that the minimal inhibitory concentration (MIC) decreased 2 to 32 times for MRSA to levofloxacin and rifampin. CONCLUSION: MRSA have qacB, qacJ and smr active efflux systems, which play a very important role in multiple antibiotic resistance.

[A multicentre study on the pathogenic agents in 665 adult patients with community-acquired pneumonia in cities of China].

OBJECTIVE: To investigate the pathogenic causes of community-acquired pneumonia (CAP) in adult patients in China, the relation of previous antibiotic use and the Pneumonia Patient Outcome Research Team (PORT) classification to microbial etiology, and the prevalence of drug resistance of common CAP bacteria. METHODS: A prospective study was performed on 665 consecutive adult patients with CAP at 12 centers in 7 Chinese cities during one year. The etiology of pneumonia was considered if one of the following criteria was met: (1) valid sputum sample yielding one or more predominant strains; (2) blood cultures yielding a bacterial pathogen; (3) seroconversion, a > or = 4-fold increase or decrease titers of antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila. Minimum inhibitory concentration (MIC) of respiratory tract isolates was determined using the agar dilution method. RESULTS: Pathogens were identified in 324/610 patients (53.1%) with valid serum samples and sputum cultures as follows: Mycoplasma pneumoniae (126, 20.7%), Streptococcus pneumoniae (63, 10.3%), Haemophilus influenzae (56, 9.2%), Chlamydia pneumoniae (40, 6.6%), Klebsiella pneumoniae (37, 6.1%), Legionella pneumophila (31, 5.1%), Staphylococcus aureus (23, 3.8%), Escherichia coli (10, 1.6%), Moraxella catarrhalis (8, 1.3%), Pseudomonas aeruginosa (6, 1.0%). Of 195 patients with a bacterial pathogen, an atypical pathogen was identified in 62 (10.2%) cases. The non-susceptibility rate of Streptococcus pneumoniae to penicillin, azithromycin, and moxifloxacin was 20.3%, 75.4% and 4.3% respectively. CONCLUSIONS: Atypical pathogens have important role in CAP, with Mycoplasma pneumoniae being the most common pathogen, and mixed infection of atypical pathogens with bacteria was found in 10.2% of the cases. Streptococcus pneumoniae and Haemophilus influenzae remain the most important bacteria for CAP. More than 75.0% of Streptococcus pneumoniae was resistant to macrolides and 20.3% was resistant to penicillin.

[A retrospective cohort study of the influence of time of hospital-acquired pneumonia onset on pathogen constitution].

OBJECTIVE: To study the influence of duration of hospitalization on etiologic agent and antibiotic-resistance of hospital-acquired pneumonia (HAP). METHODS: Cases of HAP were patients hospitalized in Fudan University Zhongshan Hospital, Ruijin Hospital, Beijing Hospital, Zhongshan University Affiliated Third Hospital, Guangzhou Medical College Affiliated Hospital and Guangdong People's Hospital. These patients were hospitalized from January 2001 to December 2003, and the diagnosis of HAP was made based on positive respiratory specimen cultures. Clinical data including time of HAP onset, severity of illness, risk factors, isolated bacteria and antimicrobial susceptibility were collected and analyzed. Statistical analysis was performed with the SPSS 12.0 software. RESULTS: A total of 562 cases of HAP were recruited, including 136 cases of early-onset pneumonia (time of onset < or = 5 d), 326 cases of middle-onset pneumonia (time of onset 6 - 14 d) and 100 cases of late-onset pneumonia (time of onset > or = 15 d). The rate of prior antibiotic use increased from 68.4% in the early-onset group to 88.0% in the late-onset group (P = 0.002); ICU admission increased from 29.4% to 46.0% (P = 0.03), and immunosuppression increased from 1.5% to 15% (P = 0.001). A total of 918 strains of bacteria were isolated, the most common pathogens being Pseudomonas aeruginosa (18.6%), Staphylococcus aureus (16.1%), Acinetobacter spp (16.1%), Klebsiella spp (14.4%) and Enterobacter spp (8.8%). Early-onset HAP were more commonly caused by Klebstella (18.3%), while the main etiologic agents for late-onset HAP were Pseudomonas aeruginosa (24.2%) and Methicillin-resistant Staphylococcus aureus (19.3%). The rates of pneumonia caused by Haemophilus and Streptococcus were 4.3% and 2.4% respectively in the early-onset cases, but none was found in late-onset cases. The antibacterial activity of ceftriaxone was influenced by duration of hospitalization, risk factors and severity of the disease. In less severe early-onset cases without risk factors, the sensitivity of ceftriaxone was 80%. But in severe late-onset cases, it was only 50%. CONCLUSIONS: There was significant difference in the pathogen constitution and antibiotic-resistance among early-onset, middle-onset and late-onset cases of HAP. The sensitivity of ceftriaxone was high in less severe early-onset cases without risk factors.

[An experimental study of the therapeutic effect of interleukin-2 and interleukin-12 with and without amphotericin B on pulmonary fungal infection].

OBJECTIVE: To study the therapeutic effect of interleukin-2 (IL-2) and interleukin-12 (IL-12) with and without amphotericin B on pulmonary fungal infection of mice. METHODS: A mouse model of pulmonary invasive aspergillus fumigatus (IPA) infection was established and the mice were divided into different groups, treated with IL-2 and IL-12 with and without amphotericin B. The survival number of mice in 15 days and the colony count of lung tissue in the different groups were observed. RESULTS: IL-2, IL-12 and amphotericin B showed synergistic effect in prolonging the survival of the infected mice and reducing the colony count in the lung tissue. CONCLUSION: IL-2 and IL-12 are effective adjuvant therapeutic agents in the immunosuppressed hosts.

[Study on the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamase-producing clinical isolates].

OBJECTIVE: To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates. METHODS: Antibiotics susceptibility was tested by E-test method, and multi-resistance plasmids were screened and isolated by extracting transformant plasmids. Inserted gene Cassettes of class 1 integron were amplified and analyzed by polymerase chain reaction (PCR) and DNA sequencing. RESULTS: Eight of the nine ESBL-producing plasmids were found to comprise class 1 integron sequence, of them 7 harbored 1 or 2 antibiotic resistant gene cassettes which encoding resistance to aminoglycosides (aacA4, aadA2 or aadA5), trimethoprim (dhfrA12 or dfrA17), rifampicin (arr-3) and chloramphenicol (cmlA6). The function of these gene cassettes corresponded to the resistance profiles of their electro-transformants. CONCLUSION: Multi-resistance gene cassettes located on plasmids and mediated by class 1 integron may play an important role in causing the development and dissemination of multiple-antibiotic resistance in ESBL-producing clinical isolates.

Combined therapy of interleukin-12 and interleukin-18 against Cryptococcus neoformans infection in a murine model.

OBJECTIVE: To explore adverse effects of combined treatment of interleukin-12 (IL-12) and interleukin-18 (IL-18) against cryptococcosis in a murine model. METHODS: Infected mice were treated with a combination of IL-12 and IL-18. Their body weight and intake of water and food were observed and recorded. Serum levels of leptin were detected with an enzyme-linked immuno sorbent assay (ELISA). RESULTS: In the combined treatment group, the intake volume of water and food were reduced, leading to weight loss and undetectable levels of leptin in the serum. These adverse effects were more profound in mice that had received higher doses of cytokines, which sometimes led to a fatal outcome. There was a significant difference compared with the control group. Neutralization of endogenous tumor necrosis factor-alpha (TNF-alpha) by its specific mAb did not alter the wasting effect of this treatment. CONCLUSIONS: The combined IL-12/IL-18 treatment may cause a number of adverse effects independent of TNF-alpha and leptin synthesis. Further investigations for resolving these adverse effects are required before clinical application of these cytokines.

[Study of susceptibility and genotype characterization of plasmid-mediated class I cephalosporinase in gram-negative bacteria].

OBJECTIVE: To investigate the susceptibility and genotype characteristics of gram-negative bacteria producing plasmid-mediated class I cephalosporinase (AmpC beta lactamase) epidemic in Southern China. METHODS: A total of 1,187 clinical isolates of nonrepetive gram-negative bacteria were collected from different cities in Southern China. AmpC beta lactamase producing isolates were identified by cefoxitin three-dimensional test, and antimicrobial susceptibility test was identified by Kirby-Bauer agar diffusion test; plasmid conjugation, plasmid extraction, universal PCR for gene amplication of corresponding group was done, and the PCR products were sequenced subsequently. RESULTS: The positive rate of cefoxitin three-dimensional test in gram-negative bacteria was 5.9% (70/1,187), and the prevalence of plasmid-mediated AmpC beta lactamase was: E. coli: 4.2% (19/451), Klebsiella: 4.7% (16/339), Enterobacter: 2.1% (4/190), Alcaligenes: 5.3% (1/19), Acinetobacter: 2.2% (1/45) and the total positive rate was: 3.5% (41/1,187). The susceptibility test showed that compared with the clinical isolates, the transconjugations remained resistance to cephamycins and ampicillin, and susceptible to cefepime and imipenem. PCR amplication and sequencing confirmed them to be bla(DHA-1) gene and bla(ACT-1) gene, and they were mainly distributed in Klebsiella and Escherichia. CONCLUSIONS: DHA-1 and ACT-1 were the most common genotypes in plasmid-mediated AmpC beta-lactamase produced by clinical isolates in Southern China. Fourth-generation cephalosporins and carbapenems could be better choices for the treatment of infection caused by AmpC betalactamase producers.