Development and implementation of a core genome multilocus sequence typing scheme for Yersinia enterocolitica: a tool for surveillance and outbreak detection.

Yersinia enterocolitica (Y. enterocolitica) is the most frequent etiological agent of yersiniosis and has been responsible for several national outbreaks in Norway and elsewhere. A standardized high-resolution method, such as core genome Multilocus Sequence Typing (cgMLST), is needed for pathogen traceability at the national and international levels. In this study, we developed and implemented a cgMLST scheme for Y. enterocolitica. We designed a cgMLST scheme in SeqSphere + using high-quality genomes from different Y. enterocolitica biotype sublineages. The scheme was validated if more than 95% of targets were found across all tested Y. enterocolitica: 563 Norwegian genomes collected between 2012 and 2022 and 327 genomes from public data sets. We applied the scheme to known outbreaks to establish a threshold for identifying major complex types (CTs) based on the number of allelic differences. The final cgMLST scheme included 2,582 genes with a median of 97.9% (interquartile range 97.6%-98.8%) targets found across all tested genomes. Analysis of outbreaks identified all outbreak strains using single linkage clustering at four allelic differences. This threshold identified 311 unique CTs in Norway, of which CT18, CT12, and CT5 were identified as the most frequently associated with outbreaks. The cgMLST scheme showed a very good performance in typing Y. enterocolitica using diverse data sources and was able to identify outbreak clusters. We recommend the implementation of this scheme nationally and internationally to facilitate Y. enterocolitica surveillance and improve outbreak response in national and cross-border outbreaks.

Predictive value of crossover sign for outcome of ultrasound-guided vacuum aspiration in women with Cesarean scar pregnancy.

OBJECTIVE: To examine the value of the crossover sign (COS) in predicting treatment outcome in women with a Cesarean scar pregnancy (CSP) who were treated with ultrasound-guided vacuum aspiration. METHODS: This was a retrospective cohort study of women with CSP who underwent ultrasound-guided vacuum aspiration. Based on the relationship between the gestational sac, Cesarean scar and anterior wall of the uterus, CSPs were classified by COS type. Analysis was conducted to investigate the association between COS type (COS-1, COS-2) and treatment outcome. The incidence of treatment failure, retained pregnancy tissue, secondary therapy and bleeding ≥ 200 mL were analyzed. RESULTS: In total, 181 eligible patients with CSP, including 90 (49.7%) women with COS-1 and 91 (50.3%) women with COS-2, were analyzed. COS-1 patients had a higher incidence of treatment failure compared with COS-2 patients (25.6% vs 8.8%; P = 0.003), as well as higher rates of retained pregnancy tissue (18.9% vs 6.6%; P = 0.013), secondary therapy (20.0% vs 6.6%; P = 0.002) and bleeding of ≥ 200 mL (13.3% vs 4.4%; P = 0.034). COS-1 and a large gestational sac (30.1-50.0 mm or >50.0 mm in diameter) were associated independently with increased risk of treatment failure (odds ratio, 4.57 (95% CI, 1.66-12.56); P = 0.003, 4.34 (95% CI, 1.35-13.94); P = 0.014 and 10.50 (95% CI, 2.54-43.46); P = 0.001, respectively). CONCLUSIONS: Ultrasound evaluation of the relationship between the gestational sac and the endometrial line (COS classification) in women with CSP may help to predict treatment outcome among those undergoing vacuum aspiration. Among COS-1 patients, especially those with a gestational sac diameter of >30.0 mm, vacuum aspiration may be discouraged. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Strictureplasty may lead to increased preference in the surgical management of Crohn's disease: a case-matched study.

BACKGROUND: Resection and strictureplasty are the two surgical modalities used in the management of Crohn's disease (CD). The objective of this study was to compare morbidity and clinical recurrence between patients who underwent strictureplasty and patients who underwent resection. METHODS: Patients with CD who underwent strictureplasty between January 2012 and December 2022 were enrolled. The patients were well matched with patients who underwent resection without strictureplasty. Patient- and disease-specific characteristics, postoperative morbidity, and clinical recurrence were also analyzed. RESULTS: A total of 118 patients who underwent a total of 192 strictureplasties were well matched to 118 patients who underwent resection. The strictureplasty group exhibited significantly less blood loss (30 ml versus 50 ml, p < 0.001) and stoma creation (2.5% versus 16.9%, p < 0.001). No significant difference was found regarding postoperative complications or length of postoperative stay. At the end of the follow-up, the overall rate of clinical recurrence was 39.4%, and no difference was observed between the two groups. Postoperative prophylactic use of biologics (odds ratio = 0.2, p < 0.001) was the only protective factor against recurrence. CONCLUSION: Strictureplasty does not increase the risk of complications or recurrence compared with resection. It represents a viable alternative to resection in selected patients, and as such, it should have a broader scope of indications and greater acceptance among surgeons.

[Safety and efficacy of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis].

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant (P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation (P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups (P>0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

[Exploration of the clinical transformation application of the artificial intelligence diagnosis system for bladder cancer based on cystoscopy].

This study aims to explore the possibility and bottleneck of clinical translation for an artificial intelligence (AI) diagnosis system for bladder cancer based on cystoscopy.We retrospectively collected videos of 101 bladder cancer patients from January to November 2023, at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among these patients, with a median age of 63 years and 81.0% were male. The bladder cancer AI diagnosis system was utilized for diagnosis, and the accuracy of diagnoses from the videos was assessed. Additionally, a surgical evaluation scale was formulated to evaluate the quality of the videos, simulating clinical usage.The final test results showed a system sensitivity of 97.8%, a positive predictive value of 81.7%, specificity of 54.2%, and a negative predictive value of 92.3%. Furthermore, the surgical evaluation scale scores ranged from 3.96 to 4.69, indicating the feasibility of clinical application for this system.This study further quantitatively validated the accuracy of an artificial intelligence system using cystoscopy videos and assessed the potential for clinical application.

[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

Prediction of knee pain improvement over two years for knee osteoarthritis using a dynamic nomogram based on MRI-derived radiomics: a proof-of-concept study.

OBJECTIVES: To develop and validate a nomogram to detect improved knee pain in osteoarthritis (OA) by integrating magnetic resonance imaging (MRI) radiomics signature of subchondral bone and clinical characteristics. METHODS: Participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. The primary outcome was 20% improvement of knee pain score over 2 years in participants administrated either vitamin D or placebo. Radiomics features of subchondral bone and clinical characteristics from 216 participants were extracted and analyzed. The participants were randomly split into the training and validation cohorts at a ratio of 8:2. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate radiomics signatures. The optimal radiomics signature and clinical indicators were fitted into a nomogram using multivariable logistic regression model. RESULTS: The nomogram showed favorable discrimination performance [AUCtraining, 0.79 (95% CI: 0.72-0.79), AUCvalidation, 0.83 (95% CI: 0.70-0.96)] as well as a good calibration. Additional contributing value of fusion radiomics signature to the nomogram was statistically significant (NRI, 0.23; IDI, 0.14, P < 0.001 in training cohort and NRI, 0.29; IDI, 0.18, P < 0.05 in validating cohort). Decision curve analysis confirmed the clinical usefulness of nomogram. CONCLUSION: The radiomics-based nomogram comprising the MR radiomics signature and clinical variables achieves a favorable predictive efficacy and accuracy in differentiating improvement in knee pain among OA patients. This proof-of-concept study provides a promising way to predict clinically meaningful outcomes.

Systemic mRNA Therapy for the Treatment of Fabry Disease: Preclinical Studies in Wild-Type Mice, Fabry Mouse Model, and Wild-Type Non-human Primates.

Fabry disease is an X-linked lysosomal storage disease caused by loss of alpha galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of globotriaosylceramide and its analogs in all cells and tissues. Although enzyme replacement therapy (ERT) is considered standard of care, the long-term effects of ERT on renal and cardiac manifestations remain uncertain and thus novel therapies are desirable. We herein report preclinical studies evaluating systemic messenger RNA (mRNA) encoding human α-Gal A in wild-type (WT) mice, α-Gal A-deficient mice, and WT non-human primates (NHPs). The pharmacokinetics and distribution of h-α-Gal A mRNA encoded protein in WT mice demonstrated prolonged half-lives of α-Gal A in tissues and plasma. Single intravenous administration of h-α-Gal A mRNA to Gla-deficient mice showed dose-dependent protein activity and substrate reduction. Moreover, long duration (up to 6 weeks) of substrate reductions in tissues and plasma were observed after a single injection. Furthermore, repeat i.v. administration of h-α-Gal A mRNA showed a sustained pharmacodynamic response and efficacy in Fabry mice model. Lastly, multiple administrations to non-human primates confirmed safety and translatability. Taken together, these studies across species demonstrate preclinical proof-of-concept of systemic mRNA therapy for the treatment of Fabry disease and this approach may be useful for other lysosomal storage disorders.

Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study.

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.

A semiparametric model for between-subject attributes: Applications to beta-diversity of microbiome data.

The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.

Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019.

We described the population structure of Bordetella pertussis (B. pertussis) in Norway from 1996 to 2019 and determined if there were evolutionary shifts and whether these correlated with changes in the childhood immunization program. We selected 180 B. pertussis isolates, 22 from the whole cell vaccine (WCV) era (1996-1997) and 158 from the acellular vaccine (ACV) era (1998-2019). We conducted whole genome sequencing and determined the distribution and frequency of allelic variants and temporal changes of ACV genes. Norwegian B. pertussis isolates were evenly distributed across a phylogenetic tree that included global strains. We identified seven different allelic profiles of ACV genes (A-F), in which profiles A1, A2, and B dominated (89%), all having pertussis toxin (ptxA) allele 1, pertussis toxin promoter (ptxP) allele 3, and pertactin (prn) allele 2 present. Isolates with ptxP1 and prn1 were not detected after 2007, whereas the prn2 allele likely emerged prior to 1972, and ptxP3 before the early 1980s. Allele conversions of ACV genes all occurred prior to the introduction of ACV. Sixteen percent of our isolates showed mutations within the prn gene. ACV and its booster doses (implemented for children in 2007 and adolescents in 2013) might have contributed to evolvement of a more uniform B. pertussis population, with recent circulating strains having ptxA1, ptxP3, and prn2 present, and an increasing number of prn mutations. These strains clearly deviate from ACV strains (ptxA1, ptxP1, prn1), and this could have implications for vaccine efficiency and, therefore, prevention and control of pertussis.

Motor cortex stimulation for chronic neuropathic pain: results of a double-blind randomized study.

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.

Association between low skeletal muscle mass and subclinical coronary atherosclerosis in asymptomatic individuals evaluated by CT.

AIM: To investigate the associations of skeletal muscle area and density with coronary atherosclerotic plaques and significant stenosis in asymptomatic adults. MATERIALS AND METHODS: A total of 243 consecutive subjects who had voluntarily undergone abdominal unenhanced computed tomography (CT) and coronary CT angiography (CCTA) as part of a general health examination were investigated retrospectively. Skeletal muscle area index (SMI) and skeletal muscle density (SMD) was assessed using CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The associations of low SMI and low SMD with coronary atherosclerotic plaques and significant stenosis were determined by logistic regression analysis. RESULTS: After adjustment for cardiovascular risk factors, there were significant associations of low SMI or low SMD with atherosclerotic plaque, total significant stenosis, and significant stenosis caused by calcified or mixed plaques (for all p<0.05). In addition, multivariate regression analysis also showed that low SMI was independently associated with calcified plaque (p=0.038) and non-calcified plaque (p=0.006), and individuals with low SMD were more likely to have mixed plaque (p=0.001). CONCLUSION: Assessment of the skeletal muscle on CT help to identify asymptomatic adults at risk for coronary atherosclerosis.

Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case-control study.

BACKGROUND: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. OBJECTIVE: To investigate the impact of early-life infections on AD development. METHODS: This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. RESULTS: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. CONCLUSION: Infections in early life are associated with AD development in infancy and early childhood.

[Clinical application of LASEREO endoscopic system in early gastric cancer].

Objective: To evaluate the clinical application of LASEREO endoscopic system in early gastric cancer (EGC). Methods: A total of 68 patients diagnosed with EGC were retrospectively analyzed between August 2017 to December 2020 in Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine. There were 50 males and 18 females finally enrolled with a median age of 64 years. EGCs were analyzed from subjective and objective aspect, as well as from magnification and non-magnification status. Six endoscopists evaluated the visibility of the EGC (RSC) and calculated the color difference (ΔEC) between EGC and the surrounding mucosa in white light imaging (WLI), blue light imaging-bright (BLI-Bri) and linked color imaging (LCI) modes. In the case of magnification (×80), the visibility of the microstructures and microvessels (RSV) was analyzed and the color difference (ΔEV) between microvessels and non-vessels areas were calculated in WLI, BLI and LCI modes. The visibility was evaluated using visibility ranking scale(RS) and the color difference (ΔE) was calculated using L*a*b* color space. Results: In WLI, BLI-Bri, and LCI modes, the mean (±SD) RSC were 2.56±0.68, 2.63±0.59 and 3.17±0.50, and the mean(±SD) ΔEC were 15.71±5.58, 12.04±3.73, and 22.84±8.46, respectively, which in LCI were higher than those in WLI and BLI-Bri modes (P<0.001).Regarding the data evaluated by senior endoscopists, the RSC was higher in BLI-Bri than that in WLI mode (2.98±0.58 vs. 2.79±0.73, P<0.001), but as to those evaluated by junior endoscopists, there were no significant differences between the WLI and BLI-Bri modes(2.29±0.72 vs. 2.23±0.72,P =0.218).In magnifying endoscopy with WLI, BLI, and LCI modes, the mean(±SD) RSV were 2.95±0.28, 3.46±0.40, and 3.38±0.33, and the mean (±SD) ΔEV were 21.68±7.52, 44.29±10.94, and 45.38±14.29, respectively.The RSV and ΔEV in LCI and BLI were higher than that in WLI mode (P<0.001). Conclusions: LCI improves the visibility of EGC by increasing ΔEC, especially in junior endoscopists. Both BLI and LCI improve the visibility of microstructures and microvessels under magnification.

[Safety and efficacy of intra-arterial tirofiban infusion in patients with acute cardiogenic cerebral embolism undergoing endovascular reperfusion therapy].

Objective: To evaluate the safety and efficacy of intra-arterial tirofiban infusion during endovascular reperfusion therapy in patients with acute cardiogenic cerebral embolism. Methods: Clinical data of 72 patients with acute cardiogenic cerebral embolism caused by large artery occlusion were retrospectively analyzed in Department of Neurology, Strategic Support Force Medical Center from August 2015 to August 2020.Among those, 52 patients were treated with intra-arterial tirofiban, the other 20 patients were treated with control medication. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality were evaluated and compared in two groups. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in tirofiban group was higher than that in control group (92.3% vs. 75.0%), but the difference was not statistically significant (P=0.104). At 90 days after operation, the rate of patients with good prognosis (mRS≤2) in tirofiban group (61.5%) was significantly higher than that in control group (35.0%) (P<0.05). The incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups (P>0.05). Conclusion: Intra-arterial tirofiban infusion in patients with acute cardiogenic cerebral embolism is effective and feasible, which improves the prognosis without increasing the risk of intracranial bleeding complications.

[Establishment and validation of a predictive model for neurogenic urinary tract injury in children].

Objective: To establish a predictive model for upper urinary tract damage in children with neurogenic bladder and verify its efficacy. Methods: From January 2011 to December 2021, 143 children with NB in the Children's Hospital of Chongqing Medical University and 84 children with NB in the First Affiliated Hospital of Zhengzhou University were selected as the research objects. The former is set as the training set and the latter is set as the validation set, and the general parameters of the two are compared. The independent risk factors of upper urinary tract damage in children with NB were screened out by Lasso regression, and multivariate logistic regression analysis and a nomogram prediction model was established. The models were validated internally and externally on the training set and validation set, respectively, and the area under the receiver operating curve (ROC) was used to verify the accuracy of the model. Results: A total of 227 children with NB were included in this study, including 121 males and 106 females, aged (10.2±3.8) years. There was no significant difference in other parameters except age between the training set and validation set (all P>0.05); Lasso regression and multivariate logistic regression analysis showed that detrusor leakage point pressure (DLPP) ≥ 40 cmH2O (OR=4.76, 95%CI: 2.01-11.26, 1 cmH2O=0.098 kPa), overactive bladder (OAB) (OR=3.08, 95%CI: 1.34-7.04), bladder compliance (BC)<20 ml/cm H2O (OR=3.65, 95%CI: 1.41-9.47), history of previous urinary tract infection (OR=2.73, 95%CI: 1.09-6.81), and abdominal pressure/other voiding patterns (OR=2.86, 95%CI: 1.20-6.82) were risk factors for upper urinary tract damage in children with NB (all P<0.05). The above parameters were used to establish a nomogram model of upper urinary tract damage in children with NB. The internal and external validation results show that the AUC values for the training and validation sets were 0.84 (95%CI: 0.77-0.91) and 0.86 (95%CI: 0.79-0.94), respectively. Conclusion: The prediction model of upper urinary tract damage in children with NB constructed in this study has high discrimination, accuracy and clinical applicability, which can help clinicians identify high-risk patients and make individualized treatment design for these patients.

[Primary orbital leiomyosarcoma: a case report].

A 20-year-old girl came to the Tianjin Medical University Eye Hospital because of progressive herniation of her right eye for 3 months. Examination revealed a huge mass behind the right eyeball, which was clinically diagnosed as a space-occupying lesion of the right orbit. Because the tumor was close to the nerve, most of the tumor was resected and pathologically diagnosed as a poorly differentiated leiomyosarcoma. Orbital evisceration was performed later. There was no recurrence during the 10-year follow-up.

[Screening of differently expressed miRNAs and the mechanism of miR-3907 in meibomian gland carcinoma].

Objective: To screen the differently expressed microRNAs (miRNAs) and to explore the effect and mechanism of microRNA-3907 (miR-3907) in meibomian gland carcinoma (MGC). Methods: Experimental research. MGC tissues and para-carcinoma tissues of patients diagnosed with MGC by histopathology were collected from July 2011 to January 2019 in Tianjin Medical University Eye Hospital. The miRNA microarray analysis of MGC and para-carcinoma tissue samples from 5 patients was performed. miR-3907 with a significant up-regulation was selected as a research object. Bioinformatics predicted and dual-luciferase gene reporter assay verified miR-3907 target genes. The protein expression levels of target genes in 18 MGC tissues and 6 para-carcinoma tissue samples were determined by immunohistochemical staining. miR-3907 over-expression, miR-3907 knock-down, target gene knock-down and miR-3907 knock-down with target gene knock-down were respectively performed in MGC cell. The mRNA and protein expressions were validated by real-time PCR and Western blotting after transfection. The cell proliferation and migration ability was detected by cell counting kit-8 and scratch experiment after transfection. The main statistical methods were Fisher's exact test, independent sample t test, two-factor repeated measure analysis of variance. Results: There were 22 differently up-regulated miRNAs and 5 differently down-regulated miRNAs in MGC tissues, of which miR-3907 was significantly up-regulated. Thrombospondin-1 (THBS1) was a target gene of miR-3907 according to bioinformatics and dual-luciferase gene reporter assay. The positive expression rate of THBS1 protein in para-carcinoma tissues (6/6) was significantly higher than that in MGC tissues (5/18), and the difference was statistically significant (P=0.003). Compared with the negative control group, the proliferation ability of the miR-3907 over-expression group was increased at 48 h and 72 h (F=3.70, 2.65; both P<0.01), and the migration rate at 24 h was significantly higher (54.6%±3.4% vs. 34.2%±0.6%; t=8.34, P<0.01). Compared with the negative control group, the proliferation ability of the miR-3907 knock-down group was decreased at 24 h, 48 h and 72 h (F=3.10, 2.17, 3.09; all P<0.05), and the migration rate at 24 h was significantly lower (40.8%±2.8% vs. 69.7%±2.7%; t=10.42, P<0.01). Compared with the negative control group, the THBS1 knock-down group promoted cell proliferation at 24 h, 48 h and 72 h (F=3.84, 3.79, 2.24; all P<0.05), and the migration rate at 24 h was significantly increased (82.5%±1.9% vs. 37.6%±5.1%; t=11.74, P<0.01). Compared with the control group, the miR-3907 knock-down with THBS1 knock-down group increased proliferation at 24 h and 48 h (F=3.97, 3.31; both P<0.05), and the migration healing rate at 24 h was significantly increased (56.9%±2.2% vs. 41.9%±4.3%; t=3.53, P<0.05). Conclusions: There are differently expressed miRNAs between MGC and para-carcinoma tissues, which may be related to the occurrence and development of MGC. miR-3907 in MGC tissues has a significant difference from that in para-carcinoma tissues. Moreover, miR-3907 can play a role in promoting proliferation and migration of MGC by inhibiting the expression of THBS1.

[Comparison study for the proportion of underdiagnosed zonulopathy in angle closure glaucoma].

Objective: To analyze the proportion and clinical characteristics of underdiagnosed zonulopathy in angle closure glaucoma (ACG) patients and to explore the related risk factors. Methods: Case-control study. Continuous cases of ACG patients who underwent phacoemulsification combined with intraocular lens implantation and goniosynechialysis surgery [ACG group, including acute angle closure glaucoma (AACG) and chronic angle closure glaucoma (CACG)] from November 1, 2020 to October 31, 2021 and age-related cataract patients who underwent phacoemulsification combined with intraocular lens implantation surgery in the same period (control group) were included. The diagnosis of zonulopathy was determined according to the intraoperative signs such as wrinkles of the anterior capsule during continuous circular capsulorhexis. The proportion of zonulopathy, preoperative diagnosis rate of zonulopathy, demographic characteristics, anterior chamber depth (ACD), axis length, difference of ACD in both eyes (ACD of the contralateral eye minus ACD of the operated eye) were compared between the two groups. The related risk factors were explored. The paired t-test (comparison between two groups of normally distributed data), non-parametric test (comparison between two groups of non-normally distributed data), Chi-square test (categorical variables), univariate and multivariate logistic regression analysis were used. Results: There were 104 ACG patients (104 eyes), including 63 AACG patients (63 eyes) and 41 CACG patients (41 eyes), and 117 controls (117 eyes). There was no significant difference in age (P=0.29) and gender (P=0.07) between the two groups. The ACG group had shallower anterior chamber (P<0.001), shorter axial length (P<0.001) and more ACD difference in both eyes (P<0.001). In the ACG group, the proportion of zonulopathy was 46.2% (48/104), which was significantly higher than that (6.0%, 7/117) in the control group (P<0.001). In the control group, only zonular laxity was found, while in the ACG group, besides the predominant zonular laxity (68.8%, 33/48), there was zonular dehiscence (31.3%, 15/48). The eyes with AACG (57.1%, 36/63) had a higher proportion of zonulopathy than those with CACG (29.3%, 12/41) (P=0.006). In the ACG group, only 14 cases (29.8%) were diagnosed preoperatively according to slit lamp examination and/or ultrasound biomicroscopy. The proportion of underdiagnosed zonulopathy was 70.8% in the ACG group (34/48). A smaller ACD was found to be related to the zonulopathy in the ACG group. All AACG cases with an ACD ≤2.0 mm and CACG cases with an ACD ≤1.9 mm had zonulopathy. Multivariate logistic regression showed that the ACD difference in both eyes (P=0.025) and the diagnosis of ACG (AACG vs. cataract, P<0.001; CACG vs. cataract, P=0.023) were independent risk factors associated with zonulopathy. Conclusions: The proportion of underdiagnosed zonulopathy among ACG patients is high. Better preoperative diagnostic methods for zonulopathy are needed. Zonulopathy is common in ACG patients, especially in AACG patients, suggesting that zonulopathy may be related to the pathogenesis of ACG. The shallower the ACD, the riskier the zonulopathy. ACD differences between two eyes and ACG types (including AACG and CACG) were related risk factors of zonulopathy.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 11, 2022).