[Geographic environment-related research advances on children's myopia: intraocular and environmental exposure factors and analytical methods].

Myopia has become a global phenomenon, transitioning into a significant public health issue of worldwide reach. The escalating prevalence of myopia may lead to an increase in the incidence of related complications, potentially resulting in irreversible vision damage for individuals. This not only causes considerable economic strain on societies but also poses a serious threat to vital sectors like national defense. This review outlines various external and internal exposure factors related to childhood myopia. It places particular focus on the analysis of the interaction between geographical environmental factors and internal exposure factors, and examines the limitations of applying traditional methods in studying the relationship between childhood myopia and geographical environmental factors. The paper also introduces two spatial regression methodologies based on frequency estimation and Bayesian estimation, summarizing their feasibility and merits when applied in the study of external exposure elements related to childhood myopia. Finally, it provides a fresh perspective on regional childhood myopia prevention strategies that are conscious of geographical environmental factors.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

[Progress on microneedle drug delivery systems for the treatment of corneal diseases].

Corneal diseases are prevalent eye conditions in China, and the lack of effective treatment in the short term can lead to blindness. However, delivering drugs to the cornea safely and effectively poses a significant challenge due to the presence of ocular barriers and clearance mechanisms. Conventional drug delivery methods exhibit low bioavailability, making it difficult to achieve therapeutic effects. Microneedles, with their ability to penetrate ocular surface barriers effectively, offer a low-invasive and highly promising drug delivery technology. This article introduces the main delivery barriers on the ocular surface, classifies microneedles, and highlights the latest developments in the treatment of corneal diseases. Finally, the potential challenges of applying microneedle delivery systems to the ocular surface are analyzed, aiming to provide insights for the clinical application of microneedles in corneal diseases.

[Mutational spectrum and its prognostic significance in childhood acute lymphoblastic leukemia based on next-generation sequencing technology].

Objective: This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia (ALL) . Methods: Targeted exome by next-generation sequencing (NGS) technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019. Correlation of genetic features and clinical features and outcomes was analyzed. Results: Among the 141 pediatric patients with ALL, 160 somatic mutations were detected in 83 patients (58.9% ) , including 37 grade Ⅰ mutations and 123 grade Ⅱ mutations. Single nucleotide variation was the most common type of mutation. KRAS was the most common mutant gene (12.5% ) , followed by NOTCH1 (11.9% ) , and NRAS (10.6% ) . RAS pathway (KRAS, FLT3, PTPN11) , PAX5 and TP53 mutations were only detected, and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found, and NOTCH1 mutation was mainly detected in T-ALL. The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL (4.16±1.33 vs 2.04±0.92, P=0.004) . The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation. There were no statistically significant differences in sex, age, newly diagnosed white blood cell count, minimal or measurable residual disease monitoring results, expected 3-year event-free survival (EFS) and overall survival (OS) between the two groups (P>0.05) . On the other hand, the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group (P=0.021 and 0.000, respectively) . Among the patients without fusion gene, the EFS of children with grade I mutation was significantly lower than children without grade I mutation (85.5% vs 100.0% , P=0.039) . Among children with B-ALL, the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation (37.5% vs 91.2% , P<0.001) . Conclusion: Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis. Therefore, targeted exome by NGS can be used as an important supplement to the traditional morphology, immunology, cytogenetics, and molecular biology classification.

Economic evaluations of interventions against influenza at workplaces: systematic review.

BACKGROUND: The burden of influenza is mostly felt by employees and employers because of increased absenteeism rates, loss of productivity and associated direct costs. Even though interventions against influenza among working adults are effective, patronage and compliance to these measures especially vaccination are low compared to other risk groups. AIMS: This study was aimed to assess evidence of economic evaluations of interventions against influenza virus infection among workers or in the workplace setting. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline for systematic reviews was followed. Three databases, PubMed, Web of Science and EconLit, were searched using keywords to identify relevant articles from inception till 25 October 2020. Original peer-reviewed papers that conducted economic evaluations of influenza interventions using cost-benefit, cost-effectiveness or cost-utility analysis methods focused on working-age adults or work settings were eligible for inclusion. Two independent teams of co-authors extracted and synthesized data from identified studies. RESULTS: Twenty-four articles were included: 21 were cost-benefit analyses and 3 examined cost-effectiveness analyses. Two papers also presented additional cost-utility analysis. Most of the studies were pharmaceutical interventions (n = 23) primarily focused on vaccination programs while one study was a non-pharmaceutical intervention examining the benefit of paid sick leave. All but two studies reported that interventions against influenza virus infection at the workplace were cost-saving and cost-effective regardless of the analytic approach. CONCLUSIONS: Further cost-effectiveness research in non-pharmaceutical interventions against influenza in workplace settings is warranted. There is a need to develop standardized methods for reporting economic evaluation methods to ensure comparability and applicability of future research findings.

Characterization of Amino Acid Substitutions in the Two-Component Regulatory System AdeRS Identified in Multidrug-Resistant Acinetobacter baumannii.

In Acinetobacter baumannii, resistance-nodulation-cell division (RND)-type efflux is a resistance mechanism of great importance since it contributes to reduced susceptibility to multiple antimicrobial compounds. Some mutations within the genes encoding the two-component regulatory system AdeRS appear to play a major role in increased expression of the RND efflux pump AdeABC and, consequently, in reduced antimicrobial susceptibility, as they are commonly observed in multidrug-resistant (MDR) A. baumannii. In the present study, the impact of frequently identified amino acid substitutions, namely, D21V and D26N in AdeR and T156M in AdeS, on adeB expression, efflux activity, and antimicrobial susceptibility was investigated. Reverse transcription-quantitative PCR (qRT-PCR) studies revealed significantly increased adeB expression caused by D26N (AdeR) and T156M (AdeS). In addition, accumulation assays have shown that these mutations induce increased efflux activity. Subsequently, antimicrobial susceptibility testing via agar dilution and broth microdilution confirmed the importance of these substitutions for the MDR phenotype, as the MICs for various antimicrobials of different classes were increased. In contrast, the amino acid substitution D21V in AdeR did not lead to increased adeB expression and did not reduce antimicrobial susceptibility. This study demonstrates the impact of the D26N (AdeR) and T156M (AdeS) amino acid substitutions, highlighting that these regulators represent promising targets for interfering with efflux activity to restore antimicrobial susceptibility. IMPORTANCE The active efflux of antimicrobials by bacteria can lead to antimicrobial resistance and persistence and can affect multiple different classes of antimicrobials. Efflux pumps are tightly regulated, and their overexpression can be mediated by changes in their regulators. Identifying these changes is one step in the direction of resistance prediction, but it also opens the possibility of targeting efflux pump regulation as a strategy to overcome antimicrobial resistance. Here, we have investigated commonly found changes in the regulators of the main efflux pumps in Acinetobacter baumannii.

[Clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia].

Objective: To investigate the clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia (B-ALL) . Methods: The clinical data of 927 newly diagnosed children with B-ALL admitted to the Fujian Medical University Union Hospital from April 2011 to May 2020 were retrospectively analyzed. According to the results of ETV6-RUNX1 gene, the patients were divided into ETV6-RUNX1(+) and ETV6-RUNX1(-) groups. The clinical features and prognosis between the two groups were compared. Among the 182 children with ETV6-RUNX1(+), 144 patients received the Chinese Childhood Leukemia Collaborative Group (CCLG) -ALL 2008 protocol (CCLG-ALL 2008 group) and 38 received the China Childhood Cancer Collaborative Group (CCCG) -ALL2015 protocol (CCCG-ALL 2015 group) . The efficacy, serious adverse effects (SAE) incidence, and treatment-related mortality (TRM) of the two groups were also compared. Results: Of the 927 B-ALL patients, 189 (20.4% ) were ETV6-RUNX1(+). The proportion of patients with risk factors (age ≥10 years or <1 year, white blood cell count ≥50×10(9)/L) in the ETV6-RUNX1(+) group was significantly lower than that in the ETV6-RUNX1(-) group (P=0.000, 0.001, respectively) , while the proportion of patients with good early response (good response to prednisone, d15 or d19 MRD <1% , and d33 or d46 MRD<0.01% in induction chemotherapy) in the ETV6-RUNX1(+) group was significantly higher than that in the ETV6-RUNX1(-) group (P=0.028, 0.004, respectively) . The 5-year EFS and OS of the ETV6-RUNX1(+) group were significantly higher than those of the ETV6-RUNX1(-) group (EFS: 89.8% vs 83.2% , P=0.003; OS: 90.2% vs 86.3% , P=0.030) . The incidence of infection-related SAE and TRM was significantly higher than that of CCCG-ALL 2015 group. A statistical difference was observed between the incidence of infection-related SAE of the two groups (27.1% vs 5.3% , P=0.004) , but no difference in TRM (4.9% vs 0, P=0.348) . Conclusion: ETV6-RUNX1(+)B-ALL children have fewer risk factors at diagnosis, better early response, lower recurrence rate, and good prognosis than that of ETV6-RUNX1(-)B-ALL children. Reducing the intensity of chemotherapy appropriately can lower the infection-related SAE and TRM and improve the long-term survival in this subtype.

Prognostic model for risk stratification of de novo metastatic nasopharyngeal carcinoma patients treated with chemotherapy followed by locoregional radiotherapy.

BACKGROUND: There is no clinically applicable prognostic model designed for patients with de novo metastatic nasopharyngeal carcinoma (mNPC) treated with chemotherapy followed by locoregional radiotherapy (LRRT). We sought to develop a predictive tool of overall survival for individualized prediction and risk stratification in this heterogeneous patient population. PATIENTS AND METHODS: A total of 244 eligible patients with de novo mNPC, who were treated with platinum-based first-line chemotherapy followed by LRRT, were included in this retrospective study. We divided patients into the training and validation sets based on the date of initial treatment, with 152 patients treated between 2008 and 2013 comprising the training set for model development and 92 patients treated at a later time (2014 to 2015) forming the validation set. We applied Cox proportional hazards model to examine factors associated with overall survival (OS). We developed and subsequently validated a prognostic model to predict OS. We assessed the performance of this prognostic model and stratified patients based on prognostic scores obtained from this proposed model. RESULTS: The median OS of the entire cohort was 60.9 months. C-creative protein, number of metastatic sites, liver metastasis, post-treatment Epstein-Barr virus DNA, and response of metastasis were significantly associated with OS. A prognostic model for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.759), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.800], and calibration, and was further validated in an independent dataset. A risk stratification derived from the model can stratify these patients into three prognostic subgroups with significantly different survival. CONCLUSION: We developed and validated a prognostic model that exhibited adequate performance in individualized prediction and risk stratification for patients with de novo mNPC treated with chemotherapy followed by LRRT.

SNHG16 promotes cell proliferation and migration through sponging miR-132 in melanoma.

Melanoma, which originates from the transformation of normal melanocytes, is one of the three main types of skin cancer. We aimed to explore the functions of SNHG16 and miR-132 in melanoma. CCK-8, Transwell assays were used to measure the viability and migration, respectively. Spearman's correlation analysis was performed to analyze the relationship between the expression of SNHG16, miR-132 and LAPTM4B in melanoma tissues. SNHG16 was overexpressed, and miR-132 was low expressed in melanoma tissues and cell lines. Moreover, overexpression of SNHG16 was associated with poor prognosis of melanoma patients. The expression of SNHG16 had a negative connection with the expression of miR-132, and it had a positive relationship with the expression of LAPTM4B in melanoma tissues. Knockdown of SNHG16 or overexpression of miR-132 inhibited SK-MEL-2 cell proliferation and migration. In addition, we confirmed that SNHG16 directly binding to miR-132 promotes the expression of LAPTM4B, facilitating the tumorigenesis of melanoma. SNHG16 promotes the expression of LAPTM4B by sponging miR-132, thereby acting as an oncogene in melanoma. This study demonstrated that the lncRNA-miRNA-mRNA signal cascade existed in melanoma, which may help elucidate the tumorigenesis and development mechanism of melanoma.

Photorefractive effect in LiNbO3-based integrated-optical circuits for continuous variable experiments.

We investigate the impact of the photorefractive effect on lithium niobate integrated quantum photonic circuits dedicated to continuous variable on-chip experiments. The circuit main building blocks, i.e. cavities, directional couplers, and periodically poled nonlinear waveguides, are studied. This work demonstrates that photorefractivity, even when its effect is weaker than spatial mode hopping, might compromise the success of on-chip quantum photonics experiments. We describe in detail the characterization methods leading to the identification of this possible issue. We also study to which extent device heating represents a viable solution to counter this effect. We focus on photorefractive effect induced by light at 775 nm, in the context of the generation of non-classical light at 1550 nm telecom wavelength.

Self-rated health scores predict mortality among people with type 2 diabetes differently across three different country groupings: findings from the ADVANCE and ADVANCE-ON trials.

AIMS: To explore whether there is a different strength of association between self-rated health and all-cause mortality in people with type 2 diabetes across three country groupings: nine countries grouped together as 'established market economies'; Asia; and Eastern Europe. METHODS: The ADVANCE trial and its post-trial follow-up were used in this study, which included 11 140 people with type 2 diabetes from 20 countries, with a median follow-up of 9.9 years. Self-rated health was reported on a 0-100 visual analogue scale. Cox proportional hazard models were fitted to estimate the relationship between the visual analogue scale score and all-cause mortality, controlling for a range of demographic and clinical risk factors. Interaction terms were used to assess whether the association between the visual analogue scale score and mortality varied across country groupings. RESULTS: The visual analogue scale score had different strengths of association with mortality in the three country groupings. A 10-point increase in visual analogue scale score was associated with a 15% (95% CI 12-18) lower mortality hazard in the established market economies, a 25% (95% CI 21-28) lower hazard in Asia, and an 8% (95% CI 3-13) lower hazard in Eastern Europe. CONCLUSIONS: Self-rated health appears to predict 10-year all-cause mortality for people with type 2 diabetes worldwide, but this relationship varies across groups of countries.

[A multivariate model for predicting induction response and prognosis in core binding factor acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors in core binding factor (CBF) acute myeloid leukemia (AML) under current therapy modalities, therefore optimizing the treatment strategies. Methods: Standard cytological and immune methods including next generation sequencing (NGS) were used for risk stratification. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were assessed by multivariate Logistic and Cox regression models in a total of 206 adults (aged 16-65 years) with CBF-AML, including 152 AML patients with t(8;21) and 54 with inv(16). Results: The CR rate of inv(16) patients after first course was 54/54(100%), significantly higher than that of t(8;21) patients [127/147(86.4%), P=0.005]. The fusion transcript level and KIT mutation were independent factors related to CR rate in t(8;21) patients (P=0.044 and 0.027; respectively). DFS and OS in inv(16) patients tended to be more superior than that in t(8;21) patients (P=0.066 for DFS; P=0.306 for OS; respectively). Multivariate Cox identified negative expression of CD(19) and female gender the independent predictors of inferior DFS in t(8;21) patients (P=0.000 for CD(19); P=0.006 for sex; respectively). Analysis of combining CD(19) with gender indicated that females/CD(1)(9-)subpopulation had significantly poor DFS than did males/CD(19)(+) ones (Bonferroni-P<0.000 01). The number of mutations in each patient, FLT3-ITD and additional karyotype abnormalities did not affect CR rate and DFS (all P>0.05). Conclusions: Patients with inv(16) have better induction response than those with t(8;21). High level of fusion transcripts and positive KIT mutation are associated with low CR rate in t(8;21) patients. Negative CD(19) expression and female gender are independent predictors of inferior DFS in t(8;21) patients.

[Comparative analysis of vertebral artery stent implantation via femoral artery and radial artery].

Objective: To study the effect and safety of vertebral artery stent implantation via femoral artery and radial artery. Methods: Twenty-four patients with vertebral artery stent implantation from December, 2017 to August, 2018 in Beijing Anzhen Hospital were randomized into 2 groups, one was research group with 12 patients, the other was control group with 12 patients. The research group underwent vertebral artery stent implantation via radial artery, the control group underwent vertebral artery stent implantation via femoral artery. The follow-up results of the two groups were analyzed. Results: The success rate of the first puncture in the research group was 100%, significantly higher than 83.33% of the control group, there was no statistical difference (χ(2)=2.528, P>0.05).The implantation time of sheath tube in the research group was (3.2±0.3) min, significantly longer than that in the control group (2.4±0.2) min, the difference was statistically significant (t=7.713, P<0.001). The time from sheath insertion to balloon dilation and bed rest time after operation in the research group were 17.3 (16.2-17.9) min, significantly less than the control group (27.1(26.1-28.3) min), the difference was statistically significant (Z=-4.157, P<0.001). The time of bed rest in the research group was 2.1 (2.0-2.2)h, significantly less than the control group (27.1(25.3- 28.9)h), the difference was statistically significant(Z=-4.167,P<0.001). No cerebrovascular events occurred during the follow-up period. One patient in the control group developed complications of vagal reflex, no patient in the research group developed complications. Conclusions: Vertebral artery stent implantation via radial artery can significantly improve the success rate and safety of the operation. Radial artery approach is a better choice for vertebral artery stent implantation.

Down-regulation of miR-1181 indicates a dismal prognosis for nasopharyngeal carcinoma and promoted cell proliferation and metastasis by modulating Wnt/ß-catenin signaling.

OBJECTIVE: Our study aimed to investigate the expression pattern, clinicopathological feature and prognostic role of miR-1181 in nasopharyngeal carcinoma (NPC), and to determine the functional effects and potential mechanism of miR-1181 in NPC. PATIENTS AND METHODS: The expression levels of miR-1181 were determined in NPC tissues and cell lines by RT-PCR. The clinical data were interpreted by chi-square test, univariate analysis, and multivariate analysis. The effect of PVT1 on proliferation was evaluated by CCK-8 and colony formation assays, and migration and invasion ability were evaluated by transwell and wound-healing assays. The association between miR-1181 and Wnt/ß-catenin pathway was analyzed by Western blot. RESULTS: We found that miR-1181 expression was significantly down-regulated in both NPC tissues and cell lines. Low expression of miR-1181 was significantly associated with N stage (p=0.013), clinical stage (p=0.037) and grade (p=0.033). Clinical assays showed that patients with low miR-1181 expression had shorter overall survival time than those with high miR-1181 expression (p=0.0007). Multivariate analysis revealed that miR-1181 expression was independently associated with the overall survival. Functional investigations indicated that overexpression of miR-1181 suppressed NPC cells proliferation, migration and invasion. Mechanistically, forced miR-1181 expression suppressed the activity of Wnt/ß-catenin pathway. CONCLUSIONS: Our findings proved that miR-1181 may serve as a candidate prognostic biomarker and target for new therapies in NPC patients.

mcr-1 facilitated selection of high-level colistin-resistant mutants in Escherichia coli.

OBJECTIVES: The mcr-1 gene is the first reported plasmid-mediated colistin resistance gene. It has caused worldwide concern about the colistin resistance in Gram-negative bacteria. The aim of this research was to study the impact of mcr-1 on the selection of high-level colistin resistance (HLCR) mutations in Escherichia coli and Klebsiella pneumoniae. METHODS: We detected the HLCR mutation rates of Enterobacteriaceae strains (K. pneumoniae XH209, KP10, and E. coli Q3, ATCC 25922) and their transformants harbouring the mcr-1 gene. Further analysis of the HLCR mutants was conducted by sequencing, plasmid elimination experiment, and real-time quantitative PCR. RESULTS: For XH209, mean mutation rate of XH209-pMCR was 1.7 (95% confidence interval (CI) 0.76-2.54) × 10-8, while XH209 and XH209-pCR2.1 showed mutation rates of 2.0 (95% CI, 1.32-2.67) × 10-8 and 2.3 (95% CI 1.47-3.13) × 10-8. For KP10 and its derived strains KP10-pCR2.1, KP10-pMCR, the mutation rates were 3.5 (95% CI 0.77-6.13) × 10-8, 4.8 (95% CI 0.69-8.94) × 10-8 and 4.2 (95% CI 0.95-7.54) × 10-8 respectively. The mutation rates of E. coli strains Q3-pMCR and ATCC25922-pMCR were 3.4 (95% CI 0.19-7.47) × 10-8 and 1.54 (95% CI 0.27-2.8) × 10-9, which were significantly higher than their corresponding non-mcr-1-carrying strains (p < 0.05). CONCLUSIONS: Beside the knowledge that mcr-1 mediates low-level colistin resistance, this gene also facilitates selection of HLCR mutants in E. coli, but does not affect K. pneumoniae.

Optimal expression and purification of sapelovirus A structural protein VP1, and its immunogenicity in mice.

Sapelovirus A (SV-A) is a positive-sense single-stranded RNA virus which is associated with acute diarrhea, pneumonia and reproductive disorders. The virus capsid is composed of four proteins, and the functions of the structural proteins are unclear. In this study, we expressed SV-A structural protein VP1 and studied its antigenicity and immunogenicity. SDS-PAGE analysis revealed that the target gene was expressed at high levels at 0.6 mM concentration of IPTG for 24 h. The mouse polyclonal antibody against SV-A VP1 protein was produced and reached a high antiserum titer (1: 2,048,000). Immunized mice sera with the recombinant SV-A VP1 protein showed specific recognition of purified VP1 protein by western blot assay and could recognize native SV-A VP1 protein in PK-15 cells infected with SV-A by indirect immunofluorescence assay. The successfully purified recombinant protein was able to preserve its antigenic determinants and the generated mouse anti-SV-A VP1 antibodies could recognize native SV-A, which may have the potential to be used to detect SV-A infection in pigs.