2019年 · 第132卷第20期

Background: Determining the Helicobacter pylori (H. pylori) infection state during the gastroscopic process is important but still challenging. The linked color imaging (LCI) technique might emphasize the mucosal color change after H. pylori infection, which might help the diagnosis. In the present study, we aimed to compare the LCI technique with traditional white light imaging (WLI) endoscopy for diagnosing active H. pylori infection. Methods: We collected and analyzed gastroscopic images from 103 patients in our hospital from November 2017 to March 2018, including both LCI and WLI modes. All images were randomly disordered and independently evaluated by four endoscopists who were blinded to the H. pylori status of patients. In addition, the H. pylori state was determined by both rapid urease test and pathology staining. The sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) were calculated for the detection of H. pylori infection. Moreover, the kappa value and interclass correlation coefficient (ICC) were used to evaluate the inter-observer variety by SPSS 24.0 software. Results: Of the 103 enrolled patients, 27 of them were positive for H. pylori infection, while the 76 patients were negative. In total, 388 endoscopic images were selected, including 197 WLI and 191 LCI. The accuracy rate for H. pylori evaluation in the corpus LCI group was significantly higher than other groups (81.2% vs. 64.3%-76.5%, χ2 = 34.852, P < 0.001). Moreover, the corpus LCI group had the optimal diagnostic power with the sensitivity of 85.41% (95% confidence interval [CI]: 76.40%-91.51%), the specificity of 79.71% (95% CI: 74.38%-84.19%), the PPV of 59.42% (95% CI: 50.72%-67.59%), and the NPV of 94.02% (95% CI: 89.95%-96.56%), respectively. The kappa values between different endoscopists were higher with LCI than with WLI (0.433-0.554 vs. 0.331-0.554). Consistently, the ICC value was also higher with LCI than with WLI (0.501 [95% CI: 0.429-0.574] vs. 0.397 [95% CI: 0.323-0.474]). We further analyzed the factors that might lead to misjudgment, revealing that active inflammation might disturb WLI judgment (accuracy rate: 58.70% vs. 76.16%, χ2 = 21.373, P < 0.001). Atrophy and intestinal metaplasia might affect the accuracy of the LCI results (accuracy rate: 66.96% vs. 73.47%, χ2 = 2.027; 68.42% vs. 73.53 %, χ2 = 1.594, respectively); however, without statistical significance (P = 0.154 and 0.207, respectively). Conclusions: The application of LCI at the corpus to identify H. pylori infection is reliable and superior to WLI. The inter-observer variability is lower with LCI than with WLI. Trial registration: Chinese Clinical Trial Registry: ChiCTR1800016730; http://www.chictr.org.cn/showproj.aspx?proj=28400

Background: Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene. This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP. Methods: We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax. Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene. Results: Among ten affected members in a multi-generational PSP kindred, with a total of 18 episodes of spontaneous pneumothorax, the median age for the initial onset of pneumothorax was 42.5 years (interquartile range: 28.8-57.2 years). Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax. A novel nonsense mutation (c.1273C>T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family. The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal tumors. Conclusions: A novel nonsense mutation of FLCN gene was found in a large family with PSP in China. Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.

Background: With the development of assisted reproductive technology (ART) and its increasing success rate in the mainland of China, more attention has been paid to the safety of ART. In this study, we explored the associations between conception by ART and pregnancy/perinatal complications, and neonatal outcomes compared with similar outcomes following spontaneous conception. Methods: This retrospective cohort study of pregnancies over a 3-year period (2013-2015) was performed at Beijing Obstetrics and Gynecology Hospital, Beijing, China. Subjects were divided into two groups: conception by ART (n = 2256) or spontaneous conception (n = 6768). According to different fertilization modes, the ART group was divided into in vitro fertilization (IVF, n = 1873) and intracytoplasmic sperm injection (ICSI, n = 383) subgroups. The ART group was also divided into two different embryo transfer methods; fresh embryo transfer (ET, n = 1583) and frozen embryo transfer (FET, n = 673) subgroups. Pregnancy complications, perinatal complications, and neonatal outcomes of the enrolled subjects were investigated and analyzed by univariate analysis and multivariate logistic regression. Results: After adjustment for maternal age, gravidity, parity, maternal education, smoking, alcohol consumption, and body mass index (BMI), pregnancies conceived by ART were associated with a significantly increased incidence of gestational diabetes mellitus (GDM; OR 1.88, 95% CI 1.56-2.27), gestational hypertension (OR 2.18, 95% CI 1.83-2.60), and intrahepatic cholestasis of pregnancy (ICP) (OR 2.79, 95% CI 2.15-3.64), compared with spontaneous conception. These associations were similar for the singleton group. In the twin group, only the incidence of ICP was significantly higher than in controls. We found that pregnancies conceived by ART were associated with perinatal complications, including placental abruption (OR 2.14, 95% CI 1.33-3.45), premature rupture of membranes (PROM; OR 1.24, 95% CI 1.06-1.45), postpartum hemorrhage (OR 2.89, 95% CI 2.33-3.59) and polyhydramnios (OR 2.01, 95% CI 1.29-3.16). The singleton group had a similar result with placental abruption, but not with fetal membranes ruptures before labor and polyhydramnios. There were no significant differences in the incidence of these perinatal complications in the twin group. Some neonatal outcomes, including preterm labor (OR 4.29, 95% CI 3.84-4.80) and low birth weight (OR 1.72, 95% CI 1.42-2.08), were more likely to occur with singleton births after ART. However, there were no significant differences for these outcomes from twin pregnancies. Perinatal complications and neonatal outcomes were consistent between the IVF and ICSI subgroups. The FET and ET subgroups showed a similar increase in complications, except for the incidence of placental abruption. After taking into account the effects of parity, birth plurality and maternal age, the ART group still exhibited increased maternal and neonatal complications, although some differences narrowed or disappeared. Conclusions: This retrospective cohort study demonstrated that patients who underwent ART were at increased risk of several adverse pregnancy outcomes compared with women who conceived spontaneously. These complications may be attributed in part to the relatively high multiple pregnancy rate after ART. Elective single embryo transfer should be promoted in China to reduce the obstetrical risks of ART pregnancy. Singletons of ART pregnancy exhibited increased maternal and neonatal complications as well, suggesting that underlying infertility or other maternal or parental factors may contribute to the adverse outcomes.

Background: Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The present study aimed to evaluate the therapeutic effect and safety of a 595-nm pulsed-dye laser (PDL) for treating facial SN in children. Methods: A total of 110 children aged 0.2 to 12 years with facial SN were treated with a 595-nm PDL in a single institution from January 2016 to February 2018. In accordance with the treatment method, the patients were retrospectively divided into the small-spot-combined-with-large-spot group (SL-group) and the large-spot group (L-group). Patients with poor therapeutic results were retreated every 6 weeks until the lesions disappeared. The minimum follow-up period was 1 year. The groups were compared using independent-samples t tests, Mann-Whitney U test, Chi-square test, and Fisher exact probability test. Results: The therapeutic efficacy was significantly higher in the SL-group than in the L-group, with clearance rates of 90.9% and 53.0% after the primary treatment, respectively (χ2= 17.937, P < 0.001). For skin lesions with a central spider body diameter ≥1 mm, the once-treatment cure rates were 100% in the SL-group and 34.8% in the L-group (χ2 = 20.780, P < 0.001). For skin lesions with a central spider body diameter <1 mm, the once-treatment cure rates were 82.6% in the SL-group and 62.8% in the L-group (χ2 = 3.961, P = 0.138). The rates of adverse reactions and recurrence did not differ between the two groups (P = 0.141 and P = 1.000, respectively). Conclusions: The 595-nm PDL might be a safe and effective treatment option for facial SN in children. The small-spot-combined-with-large-spot method is especially suitable for SN with a central spider body diameter ≥1 mm.

Background: Crohn disease is a chronic bowel disease that causes serious complications. Prevalence of Crohn disease is increasing. Studies have shown that the behavior of the disease is not stable and severe complications secondary to behavior change over time have been shown. In this study, we aimed to evaluate the prognostic risk factors associated with phenotypic change in Crohn disease in a Turkish patient cohort. Methods: Patients followed up from March 1986 to August 2011 were evaluated for demographic and clinical characteristics to determine possible risk factors and initial clinical phenotype of the disease based on the Montreal classification. The cumulative probabilities of developing stricturing or penetrating intestinal complications were estimated using the Kaplan-Meier analysis. Univariate and multivariate Cox-proportional hazard models were used to assess associations between baseline clinical characteristics and intestinal complications. Results: Three hundred and thirty patients (mean age, 30.6 ± 11.1 years; 148 female) were included in the study. Mean follow-up duration was 7.4 ± 5.3 years (range: 1.0-25.0 years). At baseline 273 patients had inflammatory-type disease, 57 patients experienced stricturing/penetrating intestinal complications before or at the time of diagnosis. The cumulative probability of developing complicated disease was 37.4% at 5 years, 54.3% at 10 years, 78.8% at 25 years. Independent predictors associated with progression to intestinal complications were current smoking, perianal disease, extra-intestinal manifestations, and location of disease. Conclusions: Location of disease is the most powerful indicator for the development of stenosis and penetrating complications in inflammatory-type disease. Patients with ileal involvement should be considered for more aggressive immunosuppressive therapy.

Background: Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance. Results: RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t= 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t= 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t= 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t= 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t= 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t= 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t= 4.12, P < 0.01). Conclusion: RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Background: Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored. Methods: BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups. Results: AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced. Conclusions: These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.

Background: Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is superior to the other. This study aimed to evaluate the safety and efficacy of ELAPE for low rectal cancer with meta-analysis. Methods: The Web of Science, Cochrane Library, Embase, and PubMed databases before September 2019 were comprehensively searched to retrieve comparative trials of ELAPE and APE for low rectal cancer. Pooled analyses of the perioperative variables, surgical complications, and oncological variables were performed. Odds ratio (OR) and mean differences (MD) from each trial were pooled using random or fixed effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary. Results: This meta-analysis included 17 studies with 4049 patients, of whom 2248 (55.5%) underwent ELAPE and 1801 (44.5%) underwent APE. There were no statistical differences regarding the circumferential resection margin positivity (13.0% vs. 16.2%, OR = 0.69, 95% CI = 0.42-1.14, P = 0.15) and post-operative perineal wound complication rate (28.9% vs. 24.1%, OR = 1.21, 95% CI = 0.75-1.94, P= 0.43). The ELAPE was associated with lower rate of intraoperative perforation (6.6% vs. 11.3%, OR = 0.50, 95% CI = 0.39-0.64, P < 0.001) and local recurrence (8.8% vs. 20.5%, OR = 0.29, 95% CI = 0.21-0.41, P < 0.001) when compared with APE. Conclusions: The ELAPE was associated with a reduction in the rate of intra-operative perforation and local recurrence, without any increase in the circumferential resection margin positivity and post-operative perineal wound complication rate when compared with APE in the surgical treatment of low rectal cancer.

Objective: Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases. Data sources: The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science. Study selection: The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. Results: CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5＇ and 3＇ ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases. Conclusions: Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.

Objective: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease of human beings characterized by not fully reversible airflow limitation. Emphysema is the main pathological feature of COPD which causes high mortality worldwide every year and consumes a large amount of medical expenses. This paper was to review the establishment and evaluation methods of animal models of emphysema or COPD, and put forward some new ideas on animal selection, method of modeling, and model evaluation. Data sources: The author retrieved information from the PubMed database up to July 2019, using various combinations of search terms, including emphysema, model, and animal. Study selection: Original articles, reviews, and other articles were searched and reviewed for animal models of emphysema. Results: This review summarized animal models of emphysema from the perspectives of animal selection, emphysema mechanism, modeling method and model evaluation, and found that passive smoking is the classic method for developing animal model of emphysema, mice are more suitable for experimental study on emphysema. Compared with pulmonary function indicators, airway inflammation indicators and oxidative stress indicators, pathomorphological indicators of lung tissue are the most important parameters for evaluating the establishment of the animal model of emphysema. Conclusions: Mice model induced by passive smoking is the classic animal model of emphysema. Pathomorphological indicators are the most important parameters for evaluating the establishment of the animal model of emphysema.

Objective: Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein, acidic, and rich in cysteine-related modular calcium-binding protein family and include two isoforms, SMOC1 and SMOC2, in humans. Functionally, SMOCs bind to calcium for various cell functions. In this review, we provided a summary of the most recent advancements and findings of SMOC1 and SMOC2 in development, homeostasis, and disease states. Data sources: All publications in the PubMed database were searched and retrieved (up to July 24, 2019) using various combinations of keywords searching, including SMOC1, SMOC2, and diseases. Study selection: All original studies and review articles of SMOCs in human diseases and embryo development written in English were retrieved and included. Results: SMOC1 and SMOC2 regulate embryonic development, cell homeostasis, and disease pathophysiology. They play an important role in the regulation of cell cycle progression, cell attachment to the extracellular matrix, tissue fibrosis, calcification, angiogenesis, birth defects, and cancer development. Conclusions: SMOC1 and SMOC2 are critical regulators of many cell biological processes and potential therapeutic targets for the control of human cancers and birth defects.