[Effects and mechanism of annexin A1-overexpressing human adipose-derived mesenchymal stem cells in the treatment of mice with acute respiratory distress syndrome].

Objective: To explore the effects and mechanism of annexin A1 (ANXA1)-overexpressing human adipose-derived mesenchymal stem cells (AMSCs) in the treatment of mice with acute respiratory distress syndrome (ARDS). Methods: The experimental study method was adopted. After the adult AMSCs were identified by flow cytometry, the 3rd passage cells were selected for the follow-up experiments. According to the random number table (the same grouping method below), the cells were divided into ANXA1-overexpressing group transfected with plasmid containing RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. The other cells were divided into ANXA1-knockdown group transfected with plasmid containing small interfering RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. At post transfection hour (PTH) 72, the fluorescence expression was observed under a fluorescence microscope imaging system, and the protein and mRNA expressions of ANXA1 were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction respectively (with the sample numbers being 3). Fifty male C57BL/6J mice aged 6-8 weeks were divided into sham injury group, ARDS alone group, normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group, with 10 mice in each group. Mice in the last 4 groups were treated with endotoxin/lipopolysaccharide to make ARDS lung injury model, and mice in sham injury group were simulated to cause false injury. Immediately after injury, mice in sham injury group and ARDS alone group were injected with normal saline through the tail vein, while mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group were injected with normal AMSCs, ANXA1-overexpressing AMSCs, and ANXA1-knockdown AMSCs, correspondingly. At post injection hour (PIH) 24, 5 mice in each group were selected, the Evans blue staining was performed to observe the gross staining of the right lung tissue, and the absorbance value of bronchoalveolar lavage fluid (BALF) supernatant of left lung was detected by microplate reader to evaluate the pulmonary vascular permeability. Three days after injection, the remaining 5 mice in each group were taken, the right lung tissue was collected for hematoxylin-eosin staining to observe the pathological changes and immunohistochemical staining to observe the CD11b and F4/80 positive macrophages, and the levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1ß in BALF supernatant of left lung were determined by enzyme-linked immunosorbent assay. Data were statistically analyzed with paired sample t test, one-way analysis of variance, and least significant difference test. Results: At PTH 72, AMSCs in both ANXA1-overexpressing group and ANXA1-knockdown group expressed higher fluorescence intensity than AMSCs in corresponding no-load control group, respectively. At PTH 72, compared with those in corresponding no-load control group, the protein and mRNA expressions of ANXA1 in ANXA1-overexpressing group were significantly increased (wth t values of 249.80 and 6.56, respectively, P<0.05), while the protein and mRNA expressions of ANXA1 in ANXA1-knockdown group were significantly decreased (wth t values of 176.50 and 18.18, respectively, P<0.05). At PIH 24, compared with those in sham injury group (with the absorbance value of BALF supernatant being 0.041±0.009), the lung tissue of mice in ARDS alone group was obviously blue-stained and the absorbance value of BALF supernatant (0.126±0.022) was significantly increased (P<0.05). Compared with those in ARDS alone group, the degree of blue-staining in lung tissue of mice was significantly reduced in normal cell group or ANXA1-overexpressing group, and the absorbance values of BALF supernatant (0.095±0.020 and 0.069±0.015) were significantly decreased (P<0.05), but the degree of blue-staining in lung tissue and the absorbance value of BALF supernatant (0.109±0.016, P>0.05) of mice in ANXA1-knockdown group had no significant change. Compared with that in normal cell group, the absorbance value of BALF supernatant of mice in ANXA1-overexpressing group was significantly decreased (P<0.05). Three days after injection, the lung tissue structure of mice in ARDS alone group was significantly damaged compared with that in sham injury group. Compared with those in ARDS alone group, hemorrhage, infiltration of inflammatory cells, alveolar collapse, and interstitial widening in the lung tissue of mice were significantly alleviated in normal cell group and ANXA1-overexpressing group, while no significant improvement of above-mentioned lung tissue manifestation was observed in ANXA1-knockdown group. Three days after injection, the numbers of CD11b and F4/80 positive macrophages in the lung tissue of mice in ARDS alone group were significantly increased compared with those in sham injury group. Compared with those in ARDS alone group, the numbers of CD11b and F4/80 positive macrophages in lung tissue of mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group reduced, with the most significant reduction in ANXA1-overexpressing group. Three days after injection, compared with those in sham injury group, the levels of TNF-α, IL-6, and IL-1ß in BALF supernatant of mice in ARDS alone group were significantly increased (P<0.05). Compared with those in ARDS alone group, the levels of TNF-α, IL-6, and IL-1ß in BALF supernatant of mice in normal cell group and ANXA1-overexpressing group, as well as the level of IL-1ß in BALF supernatant of mice in ANXA1-knockdown group were significantly decreased (P<0.05). Compared with that in normal cell group, the level of TNF-α in BALF supernatant of mice was significantly decreased in ANXA1-overexpressing group (P<0.05) but significantly increased in ANXA1-knockdown group (P<0.05). Conclusions: Overexpression of ANXA1 can optimize the efficacy of AMSCs in treating ARDS and enhance the effects of these cells in inhibiting inflammatory response and improving pulmonary vascular permeability, thereby alleviating lung injury of mice with ARDS.

Sleep Disturbance Among Adults With Overactive Bladder: A Cross-sectional Survey.

OBJECTIVE: To examine differences in sleep disturbance, nocturia, and depression among adults with overactive bladder (OAB) by treatment type. METHODS: A cross-sectional survey of adults with OAB assessed sleep disturbance, nocturia, and depression using patient-reported outcome measures, including the Patient Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.1 (Sleep Disturbance and Depression domains), Lower Urinary Tract Dysfunction Research Network Symptom Index-10, and PROMIS Sleep Disturbance Short Form 8B. Treatment groups included antimuscarinics, ß-3 adrenergic agonists, and no treatment. Analysis of covariance (ANCOVA) was used to test for differences in study endpoints; Bonferroni-adjusted pairwise tests (P < .05/3) were performed to compare differences in least squares means between groups. RESULTS: One hundred participants were included per treatment group. The overall mean (standard deviation) age across all groups was 47.8 (11.8) years. Symptom scores across all PROMIS domains in all three treatment groups were higher than the US general population. There were no statistically significant differences in outcomes across treatment groups. CONCLUSION: Adults with OAB reported being affected by sleep disturbance and depression, regardless of treatment. The mirabegron group trended toward the lowest symptom impact across all outcomes, however, comparisons were not significant. Future research should examine temporal associations between OAB treatment, sleep disturbance, and outcomes.

[QUADAS-C-A tool for assessing risk of bias regarding Quality Assessment of Diagnostic Accuracy Studies-Comparative].

This paper introduced the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), illustrated the comparison with the QUADAS-2, and using QUADAS-C together with QUADAS-2 to present QUADAS-C results through systematic reviews. Like the domain for QUADAS-2, QUADAS-C retained four domains, including patient selection, index test, reference standard, flow, and timing, and comprised additional questions for each QUADAS-2 part. Unlike the QUADAS-2 tool, the starting question of each domain for QUADAS-C was designed to summarize the risk of biased information captured by QUADAS-2. QUADAS-C only dealt with the risk of bias but did not include the part of concerns regarding applicability. The answers to signaling questions for each domain of QUADAS-C would lead to a 'low''high' or 'unclear' risk of biased judgment for the original study.

Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Assessing somatization in urologic chronic pelvic pain syndrome.

BACKGROUND: This study examined the prevalence of somatization disorder in Urological Chronic Pelvic Pain Syndrome (UCPPS) and the utility of two self-report symptom screening tools for assessment of somatization in patients with UCPPS. METHODS: The study sample included 65 patients with UCPPS who enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Study at Washington University. Patients completed the PolySymptomatic PolySyndromic Questionnaire (PSPS-Q) (n = 64) and the Patient Health Questionnaire-15 Somatic Symptom Severity Scale (PHQ-15) (n = 50). Review of patient medical records found that only 47% (n = 30) contained sufficient documentation to assess Perley-Guze criteria for somatization disorder. RESULTS: Few (only 6.5%) of the UCPPS sample met Perley-Guze criteria for definite somatization disorder. Perley-Guze somatization disorder was predicted by definite PSPS-Q somatization with at least 75% sensitivity and specificity. Perley-Guze somatization disorder was predicted by severe (> 15) PHQ-15 threshold that had > 90% sensitivity and specificity but was met by only 16% of patients. The moderate (> 10) PHQ-15 threshold had higher sensitivity (100%) but lower specificity (52%) and was met by 52% of the sample. CONCLUSIONS: The PHQ-15 is brief, but it measures symptoms constituting only one dimension of somatization. The PSPS-Q uniquely captures two conceptual dimensions inherent in the definition of somatization disorder, both number of symptoms and symptom distribution across multiple organ systems, with relevance for UCPPS as a syndrome that is not just a collection of urological symptoms but a broader syndrome with symptoms extending beyond the urological system.

Characterization of facial asymmetry in skeletal Class III malocclusion and its implications for treatment.

Jaw deviation is frequently seen in Class III patients. The aim of the study was to investigate asymmetric features of skeletal, dental and soft tissues in three types of jaw asymmetry based on our previously reported classification system. The cone-beam computed tomography (CBCT) images of 70 Class III patients were analysed. Group 1 patients showed large shift of menton and synchronous but smaller ramus deviation. The maxillomandibular complex had roll and yaw rotations to the menton-deviation side. Maxillary and dental asymmetry was obvious in transverse and vertical dimensions. Cant of occlusal plane and lip line was apparent. Group 2 patients also exhibited menton and ramus deviation to the same side but the discrepancy in ramus width was larger than menton shift. Asymmetry in Group 2 resulted from a bodily side shift of the maxillomandibular complex without obvious rotation. Group 3 patients had menton and ramus deviated in opposite directions which seemed secondary to a yaw rotation. Double-jaw surgery is generally required for Groups 1 and 3 while Group 2 patients may be successfully treated by mandibular surgery only provided that arch width discrepancy can be managed by orthodontic measures.

Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a comparative study of lipophilic and hydrophilic drugs.

The influence of an erbium:YAG laser on the transdermal delivery of drugs across skin was studied in vitro. Indomethacin and nalbuphine, which have the same molecular weight, were selected as model lipophilic and hydrophilic drugs, respectively, to compare skin permeation by laser treatment. The results indicate a significant increase in the permeation of indomethacin and nalbuphine across skin pretreated with an erbium:YAG laser. The laser had a greater effect on the permeation of hydrophilic molecules which usually possess low permeability. The laser intensity and its spot size were found to play an important role in controlling transdermal delivery of drugs. Permeation of the hydrophilic drug increased following an increase of laser energy. On the other hand, a different result was observed for the lipophilic drug transported across laser-treated skin. The stratum corneum (SC) layer in skin could be partly ablated by the erbium:YAG laser. The barrier function of the SC may also be modulated by a lower intensity of the laser without affecting the viability and structure of the epidermis/dermis as determined by histological observations. However, ultrastructural alteration of the epidermis/dermis may be caused by laser treatment. Use of an erbium:YAG laser is a good method for enhancing transdermal absorption of both lipophilic and hydrophilic drugs, because it allows precise control of SC removal, and this ablation of SC can be reversible to the original normal status.

Suppression effect of soy isoflavones on nitric oxide production in RAW 264.7 macrophages.

Genistein, daidzein, and glycitein, as primary isoflavones in soybeans, are reported to have beneficial effects on atherosclerosis, chronic inflammatory diseases, and cancers that are conducted by nitric oxide (NO) injury. The objectives of this study were to investigate the effects and mechanisms of these soy isoflavones on the inducible nitric oxide synthase (iNOS) system in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Genistein, daidzein, and glycitein dose-dependently suppress NO production (IC(50) = 50 microM) in supernatants of LPS-activated macrophages as measured on the basis of nitrite accumulation. In addition, direct inhibition of iNOS activity, determined by means of the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, and markedly reduced iNOS protein and mRNA levels, evaluated by means of Western blot and RT-PCR, respectively, were found in homogenates of LPS-activated cells treated with each isoflavone. Moreover, genistein was found to have a greater inhibitory effect on NO production but no significant effect on iNOS activity or protein and gene expression to daidzein and glycitein. These observations reveal that the suppression of NO production by genistein, daidzein, and glycitein might be due to the inhibition of both the activity and expression of iNOS in LPS-activated macrophages. The result suggests that soy isoflavones might attenuate excessive NO generation at inflammatory sites.

Acrokeratosis paraneoplastica (Bazex syndrome) with adenocarcinoma of the colon: report of a case and review of the literature.

Acrokeratosis paraneoplastica is a rare disease and is uncommon even in patients with upper aerodigestive tract cancer. We report a 63-year-old man with a 1-month history of numerous pruritic lesions and vesicles on both feet. Although he had received local therapy, progressive dense scale formation involving both palms and both soles was found. Colonoscopy was performed because of hematochezia, and it revealed an early colon cancer. After the resection of the cancer, the skin lesions began to fall off dramatically. To the best of our knowledge, there is no report of acrokeratosis paraneoplastica associated with colon cancer in the literature. This is the first case report of acrokeratosis paraneoplastica associated with early colon cancer.

High-risk human papillomavirus deoxyribonucleic acid as an adjunct marker in cervical cytology.

BACKGROUND: This study was designed to determine whether screening for high-risk human papillomaviruses testing could improve the detection of cervical dysplasia and cancer in assistance with conventional Papanicoloau (Pap) smears. METHODS: The study was based on 114 patients with abnormal Pap smears referred for colposcopy from Feb. 1997 to Dec. 1997. The presence of high-risk human papillomavirus (HPV) DNA was determined with the Hybrid Capture method (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Cytologic examination by Papanicolaou smear was based on the Bethesda system and cervical biopsy was done via colposcopy. RESULTS: Cytologic examination demonstrated high-grade squamous intraepithelial lesions (HSIL) in 24 patients with HPV positive (75%), low-grade squamous intraepithelial lesions (LSIL) in 38 with 61% HPV positive, and atypical squamous cells of undetermined significance (ASCUS) in 52 with 37% HPV positive. Among patients with a cytologic diagnosis of borderline abnormalities (ASCUS or LSIL), those with who were HPV positive were significantly more likely to have cervical dysplasia (both p < 0.05). The sensitivity of combined HPV assay and/or cytology for detection of noninvasive precursor (91%) was significantly greater than those of cytology (68%) or HPV assay (81%) alone. CONCLUSION: The addition of the hybrid capture high-risk HPV DNA assay to cytologic examination of cervical smears appears to increase the sensitivity of cervical screening. Our findings suggest that HPV DNA may be a useful adjunct marker for early detection of cervical dysplasia in women with minimally abnormal Pap smears (ASCUS/low-grade SIL).

Phe-46(CD4) orients the distal histidine for hydrogen bonding to bound ligands in sperm whale myoglobin.

The role of Phe-46(CD4) in modulating the functional properties of sperm whale myoglobin was investigated by replacing this residue with Leu, Ile, Val, Ala, Trp, Tyr, and Glu. This highly conserved amino acid almost makes direct contact with the distal histidine and has been postulated to affect ligand binding. The overall association rate constants for CO, O2, and NO binding were little affected by decreasing the size of residue 46 step-wise from Phe to Leu to Val to Ala. In contrast, the rates of CO, O2, and NO dissociation increased 4-, 10-, and 25-fold, respectively, for the same series of mutants, causing large decreases in the affinity of myoglobin for all three diatomic gases. The rates of autooxidation at 37 degrees C, pH 7.0 increased dramatically from approximately 0.1-0.3 h-1 for wild-type, Tyr-46, and Trp-46 myoglobins to 1.5, 5.2, 4.9, and 5.0 h-1 for the Leu-46, Ile-46, Val-46 and Ala-46 mutants, respectively. Rates of NO and O2 geminate recombination were measured using 35 ps and 9 ns laser excitation pulses. Decreasing the size of residue 46 causes significant decreases in the extent of both picosecond and nanosecond rebinding processes. High resolution structures of Leu-46 and Val-46 metmyoglobins, Val-46 CO-myoglobin, and Val-46 deoxymyoglobin were determined by X-ray crystallography. When Phe-46 is replaced by Val, the loss of internal packing volume is compensated by (1) contraction of the CD corner toward the core of the protein, (2) movement of the E-helix toward the mutation site, (3) greater exposure of the distal pocket to intruding solvent molecules, and (4) large disorder in the position of the side chain of the distal histidine (His-64). In wild-type myoglobin, the van der Waals contact between C zeta of Phe-46 and C beta of His-64 appears to restrict rotation of the imidazole side chain. Insertion of Val at position 46 relieves this steric restriction, allowing the imidazole side chain to rotate about the C alpha - C beta bond toward the surface of the globin and about the C beta - C gamma bond toward the space previously occupied by the native Phe-46 side chain. This movement disrupts hydrogen bonding with bound ligands, causing significant decreases in affinity, and opens the distal pocket to solvent water molecules, causing marked increases in the rate of autooxidation.(ABSTRACT TRUNCATED AT 400 WORDS)

Urinary N-acetyl-glucosaminidase excretion and environmental lead exposure. Green Cross Health Service Association Study Group.

To understand the relationship between chronic low-level lead exposure and renal function, residents living nearby a lead battery factory for more than 10 years were selected and entered in this cross-section study. The residents living in the 1st village, within 500 m from the factory, were grouped in group 1; those in the 2nd village, within 1,000-1,500 m, in group 2, and those in the 3rd village, far from any lead-contaminated sources, in group 3. Twenty-four-hour urinary N-acetyl-glucosaminidase (NAG) was detected as early indicator of renal damage, and an ethylenediamine-tetraacetic acid mobilization test was performed to estimate total body lead burden of lead-exposed persons. Blood lead level (BLL) showed a significant difference among the three study groups. The further the distance between the group and the factory, the higher BLL. The results showed a significant high prevalence of abnormal urine NAG excretion in the chronic lead-exposed group, although BLL and body lead burden of these persons were within the 'normal' range. A significant correlation between body lead burden less than 200 micrograms and 24-hour urine NAG excretion and a dose-response relationship between them were found. These observations suggested that lead was the possible cause of abnormal renal tubular function in persons with chronic low-level lead exposure, but this effect became blunt when body lead burden was more than 200 micrograms. The possible explanation may be that high body lead burden from long-term exposure will deplete the kidney of NAG or render it insensitive to the effects of lead exposure.(ABSTRACT TRUNCATED AT 250 WORDS)