[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

Autonomous Artificial Intelligence Increases Access and Health Equity in Underserved Populations with Diabetes.

Diabetic eye disease (DED) is a leading cause of blindness in the world. Early detection and treatment of DED have been shown to be both sight-saving and cost-effective. As such, annual testing for DED is recommended for adults with diabetes and is a Healthcare Effectiveness Data and Information Set (HEDIS) measure. However, adherence to this guideline has historically been low, and access to this sight-saving intervention has particularly been limited for specific populations, such as Black or African American patients. In 2018, the US Food and Drug Agency (FDA) De Novo cleared autonomous artificial intelligence (AI) for diagnosing DED in a primary care setting. In 2020, Johns Hopkins Medicine (JHM), an integrated healthcare system with over 30 primary care sites, began deploying autonomous AI for DED testing in some of its primary care clinics. In this retrospective study, we aimed to determine whether autonomous AI implementation was associated with increased adherence to annual DED testing, and whether this was different for specific populations. JHM primary care sites were categorized as "non-AI" sites (sites with no autonomous AI deployment over the study period and where patients are referred to eyecare for DED testing) or "AI-switched" sites (sites that did not have autonomous AI testing in 2019 but did by 2021). We conducted a difference-in-difference analysis using a logistic regression model to compare change in adherence rates from 2019 to 2021 between non-AI and AI-switched sites. Our study included all adult patients with diabetes managed within our health system (17,674 patients for the 2019 cohort and 17,590 patients for the 2021 cohort) and has three major findings. First, after controlling for a wide range of potential confounders, our regression analysis demonstrated that the odds ratio of adherence at AI-switched sites was 36% higher than that of non-AI sites, suggesting that there was a higher increase in DED testing between 2019 and 2021 at AI-switched sites than at non-AI sites. Second, our data suggested autonomous AI improved access for historically disadvantaged populations. The adherence rate for Black/African Americans increased by 11.9% within AI-switched sites whereas it decreased by 1.2% within non-AI sites over the same time frame. Third, the data suggest that autonomous AI improved health equity by closing care gaps. For example, in 2019, a large adherence rate gap existed between Asian Americans and Black/African Americans (61.1% vs. 45.5%). This 15.6% gap shrank to 3.5% by 2021. In summary, our real-world deployment results in a large integrated healthcare system suggest that autonomous AI improves adherence to a HEDIS measure, patient access, and health equity for patients with diabetes - particularly in historically disadvantaged patient groups. While our findings are encouraging, they will need to be replicated and validated in a prospective manner across more diverse settings.

Use of Diabetes Technologies and Retinopathy in Adults With Type 1 Diabetes.

Importance: Diabetic retinopathy (DR) is a complication of diabetes that can lead to vision loss. Outcomes of continuous glucose monitoring (CGM) and insulin pump use in DR are not well understood. Objective: To assess the use of CGM, insulin pump, or both, and DR and proliferative diabetic retinopathy (PDR) in adults with type 1 diabetes (T1D). Design, Setting, and Participants: A retrospective cohort study of adults with T1D in a tertiary diabetes center and ophthalmology center was conducted from 2013 to 2021, with data analysis performed from June 2022 to April 2023. Exposure: Use of diabetes technologies, including insulin pump, CGM, and both CGM and insulin pump. Main Outcomes and Measures: The primary outcome was development of DR or PDR. A secondary outcome was the progression of DR for patients in the longitudinal cohort. Multivariable logistic regression models assessed for development of DR and PDR and association with CGM and insulin pump use. Results: A total of 550 adults with T1D were included (median age, 40 [IQR, 28-54] years; 54.4% female; 24.5% Black or African American; and 68.4% White), with a median duration of diabetes of 20 (IQR, 10-30) years, and median hemoglobin A1c (HbA1c) of 7.8% (IQR, 7.0%-8.9%). Overall, 62.7% patients used CGM, 58.2% used an insulin pump, and 47.5% used both; 44% (244 of 550) of the participants had DR at any point during the study. On univariate analysis, CGM use was associated with lower odds of DR and PDR, and CGM with pump was associated with lower odds of PDR (all P < .05), compared with no CGM use. Multivariable logistic regression adjusting for age, sex, race and ethnicity, diabetes duration, microvascular and macrovascular complications, insurance type, and mean HbA1c, showed that CGM was associated with lower odds of DR (odds ratio [OR], 0.52; 95% CI, 0.32-0.84; P = .008) and PDR (OR, 0.42; 95% CI, 0.23-0.75; P = .004), compared with no CGM use. In the longitudinal analysis of participants without baseline PDR, 79 of 363 patients (21.8%) had progression of DR during the study. Conclusions and Relevance: In this cohort study of adults with T1D, CGM use was associated with lower odds of developing DR and PDR, even after adjusting for HbA1c. These findings suggest that CGM may be useful for diabetes management to mitigate risk for DR and PDR.

[Establishment and verification of invasion syndrome prediction model in patients with diabetes complicated with Klebsiella pneumoniae liver abscess].

Objective: To analyze the correlative factors of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and to construct and verify the online nomographic prediction model. Methods: A case control study. The clinical data of 213 diabetic patients with Klebsiella pneumoniae liver abscess admitted to the Third Affiliated Hospital of Soochow University from January 1, 2015 to December 31, 2021 were retrospectively analyzed. The patients were divided into the training set (149 cases) and the test set (64 cases) by stratified random sampling method at a ratio of 7∶3. Synthetic minority over-sampling technique(SMOTE) was used to process the imbalanced data, then Lasso regression was used to screen out the optimal feature variables in the training set and multivariate logistic regression model was used to construct the prediction model of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and verify it in the training set and test set. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the prediction efficiency of the model, and the simple and online interactive dynamic web page column graph was constructed. Results: Among the 213 patients, 60 were males and 153 were females, aged of (61.4±12.0) years. A total of 25(11.74%) diabetic patients with Klebsiella pneumoniae liver abscess developed invasion syndrome, which were included in divided into invasive K.pneumoniae liver abscesses syndrome (IKPLAS) group, and the other 188 cases were in without invasive K.pneumoniae liver abscesses syndrome (NIKPLAS) group. SMOTE algorithm was used for oversampling processing, so that the ratio of positive and negative samples was 1∶1. In the oversampling training set, 5 main risk factors were screened based on Lasso regression, namely fasting blood glucose (λ=0.063), hemoglobin (λ=-0.042), blood urea nitrogen (λ=-0.050), abscess size (λ=-0.025) and sequential organ failure assessment (SOFA) score (λ=0.450), respectively. Multivariate logistic regression model showed that fasting blood glucose (OR=1.20, 95%CI: 0.98-1.48, P=0.006), hemoglobin (OR=0.90, 95%CI: 0.86-0.95, P<0.001), blood urea nitrogen (OR=1.22, 95%CI: 1.03-1.43, P=0.017), abscess diameter (OR=0.76, 95%CI: 0.61-0.94, P=0.010), SOFA score (OR=3.08, 95%CI: 2.18-4.36, P<0.001) were associated with invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The area under the curve of ROC in the training set was 0.966 (95%CI: 0.943-0.989), the sensitivity was 90.5%, and the specificity was 91.3%. The area under the curve of the validation set ROC was 0.946 (95%CI: 0.902-0.991), with a sensitivity of 79.6% and a specificity of 88.9%. The calibration curves drawn in the training set and the test set fit well with the ideal curve. DCA showed that the neomorph prediction model had a good clinical net benefit when predicting the risk of IKPLAS in patients with diabetes complicated with Klebsiella pneumoniae liver abscess was 0.10-0.40. Conclusions: Fasting blood glucose, hemoglobin, urea nitrogen, abscess size and SOFA score are the related factors for invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The constructed column graph can effectively predict the risk of invasion syndrome in patients with diabetes complicated with Klebsiae pneumoniae liver abscess.

Electro/Ni Dual-Catalyzed Decarboxylative C(sp3)-C(sp2) Cross-Coupling Reactions of Carboxylates and Aryl Bromide.

Paired redox-neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non-toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C-C cross-coupling reactions. Here, we report the electro/Ni dual-catalyzed redox-neutral decarboxylative C(sp3)-C(sp2) cross-coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar-Br bond by a NiI-bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2-phenoxy propionic acid, undergo oxidative decarboxylation to form carbon-based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)-C(sp2) cross-coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual-catalyzed cross-coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)-C(sp2) cross-coupling and represent a promising method for the construction of the C(sp3)-C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow-synthesis technology.

Frequency and distribution of ophthalmic surgical procedures among patients with inherited retinal diseases.

OBJECTIVE OR PURPOSE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects 18 years and older who were followed at the Johns Hopkins Genetic Eye Disease (GEDi) Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into two groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURE: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n=180/230) had a history of more than one surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by YAG capsulotomy, refractive surgery, retinal surgery, and others. CEIOL occurred more frequently in RP than in MCCRD subjects (POR 2.59, p = 0.002). RP subjects underwent CEIOL at a younger age than MCCRD patients (HR = 2.11, p < 0.001). CONCLUSION: Approximately one-third of IRD patients had a history of laser or incisional surgery. CEIOL was the most common surgery; its frequency and timing may be associated with IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery.

[Research on quantitative evaluation of revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004)].

Objective: To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard. Methods: From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation. Results: A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant (M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items (r(s)=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion: GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

[Study on the implementation effect evaluation of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004)].

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

[Introduction to carcinogenesis of nickel compounds in ILO criteria for Diagnosis and Exposure Standard for Occupational Diseases].

International Agency for Research on Cancer (IARC) classifies nickel compounds as Class Ⅰ carcinogens. International Labour Organization (ILO) also lists nickel compounds as carcinogenic factors of occupational cancer. At present, China is revising the Classification and Catalogue of Occupational Diseases, and cancer caused by nickel compounds may also be included in the statutory occupational diseases. The Diagnostic and Exposure Standards for Occupational Diseases published by ILO in 2022 discussed the pathogenic characteristics, occupational exposure, main health effects, diagnostic criteria and key preventive measures of nickel compounds in detail. This article mainly introduces its contents, in order to provid a basis for the formulation of relevant standards in China.

Effects of different stocking densities on the development of reproductive and immune functions in young breeder pigeons during the rearing period.

1. Stocking density (SD) is closely related to animal performance. This experiment was designed to evaluate the development of reproductive and immune functions of young pigeons under different SDs.2. A total of 288 (half male and half female) 40-day-old pigeons (body weight 400 ± 15 g) were allocated into four groups: High stocking density (HSD; 0.308 m3/bird), standard stocking density (SD; 0.616 m3/bird), and low stocking density (LSD; 1.232 m3/bird) and a caged (control; 0.04125 m3/bird). Every group had six replicates of the same sex.3. The results showed that caged male pigeons had the highest testis index, testosterone content, and gene expression of the androgen receptor gene. LSD treatment induced the highest concentrations of oestradiol, progesterone and mRNA levels of reproductive hormone receptor genes in female pigeons. In male pigeons, the spleen index (organ weight calculated as a percentage of total body weight) showed a peak level (0.09 ± 0.020) in the LSD group, and the thymus index peaked (0.23 ± 0.039) in SD group. However, the index for ovary, spleen, thymus and bursa of Fabricius in female pigeons showed no significant changes among different groups.4. The IL-1ß, IL-8, IFN-γ, TGF-ß and toll-like receptor 2 (TLR-2) mRNA levels reached their maximum values in both male and female pigeon spleens in the LSD group.5. Young male pigeons housed in cages showed increased testicular development while low stocking density increased the development of reproductive function in young female pigeons. A larger activity space could help enhance the immune function of both male and female pigeons.

Retraction Note: Long non-coding RNA FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in esophageal cancer cells.

The article "Long non-coding RNA FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in esophageal cancer cells", by X.-S. Liang, Y. Sun, T. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (16): 5214-5222-DOI: 10.26355/eurrev_201808_15719-PMID: 30178844 has been retracted by the authors for the following reasons. The authors asked to retract this manuscript as they identified some problems with the data reported, and the dilution ratio of the antibody during the Western blot experimental operation is incorrect. In this article, the dilution of antibodies is described as follows: anti-cyclin D 1 (dilution 1:500, Abcam, Cambridge, MA, USA), anti-MMP7 (dilution 1:500, Santa Cruz Biotechnology, Santa Cruz, CA, USA), anti-p21 (dilution 1:400, Cell Signaling Technology, Danvers, MA, USA), anti-p-Akt (dilution 1:500, Abcam, Cambridge, MA, USA), anti-Akt (dilution 1:500, Abcam, Cambridge, MA, USA), and anti-p-actin (dilution 1:500, Santa Cruz Biotechnology, Santa Cruz, CA, USA). Nonetheless, authors affirm they only used a dilution of 1:200 for all antibodies, undermining the Western blot experimental operation. Thus, the article's conclusions are considered invalid and unreliable. This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15719.

Serum squamous cell carcinoma antigen level and magnetic resonance imaging for the prognosis of locally advanced cervical cancer.

OBJECTIVE: Squamous cell carcinoma antigen (SCC-ag) and magnetic resonance imaging (MRI) were explored to serve as biomarkers to predict the prognosis of cervical cancer (CC) patients treated with neoadjuvant chemotherapy (NACT) prior to radical surgery, with the aim of identifying the subgroup that least benefits from the combined therapy. PATIENTS AND METHODS: All patients were treated with NACT prior to radical surgery and received MRI and SCC-ag examinations before and after NACT. For these three cycles of NACT, patients were treated with intravenous paclitaxel at 150 mg/m2 over a period of 3 hours and carboplatin, with the area under the sera concentration-time curve of 5 over a period of 30 minutes on the first day of each cycle. Meanwhile, the blood pressure, ECG, and blood oxygen saturation of the patients were observed during the infusion. A discovery cohort and a validation cohort were applied to examine the prognostic performance of SCC-ag, MRI, and their combination. The endpoints of our study were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 384 patients diagnosed between August 2006 and December 2010 were enrolled in our research, with 206 patients in the discovery cohort and 178 patients in the validation cohort. The high-risk group identified by MRI had a worse OS [hazard ratio (HR), 3.567; 95% confidence interval (CI), 1.466-8.677; log-rank p=0.0027) and PFS (HR, 4.062; 95% CI, 2.171-7.6; log-rank p<0.0001) than the low-risk group. Meanwhile, the SCC-RC could serve as a strong prognostic factor to predict OS (HR, 5.614; 95% CI, 2.473-12.744; log-rank p<0.0001) and PFS (HR, 7.481; 95% CI, 4.194-13.344; log-rank p<0.0001) for CC. In addition, the combined MRI and SCC-ag had greater prognostic efficiency and were used to divide the whole patient population into three groups. Compared with patients in the low-risk group, patients in the high-risk group had a worse OS (HR, 8.216; 95% CI, 2.98-22.651; log-rank p<0.0001) and PFS (HR, 11.757; 95% CI, 5.735-24.104; log-rank p<0.0001). Multivariate analyses revealed that MRI, SCC-ag, and their combination were independent prognostic factors. CONCLUSIONS: SCC-ag and MRI, individually or in combination, were bound up with OS and PFS in CC. Additionally, the predictive efficiency improved when SCC-ag and MRI were combined in a risk model that predicted the OS and PFS of SCC compared with the predictive efficiency of either SCC-ag or MRI alone, revealing that the combination of these two biomarkers could help to ameliorate prognostic stratification and to guide personalized therapy for SCC patients.

[Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

[Clinical and prognostic characteristics of pediatric acute myeloid leukemia with myelodysplasia-related changes under different diagnostic criteria].

Objective: To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria). Methods: In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results: Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33,P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44, P=0.119). Conclusions: Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

Ten-Year Outcome of Boston Type I Keratoprosthesis Surgery at a Tertiary Care Center.

PURPOSE: The aim of this study was to report long-term outcomes of patients who have undergone Boston type I keratoprosthesis (KPro) surgery. METHODS: This study was a retrospective review. Inclusion criteria were KPro surgery between 2006 and 2012 and at least 10 years of follow-up. Demographics, ocular history, surgery indication, clinical variables, and postsurgical outcomes were recorded. Descriptive statistical analysis was performed. RESULTS: We identified 75 patients with KPro implantation, and 17 patients with at least 10 years of follow-up (median = 11.1 years; range, 10.0-12.8 years) were included. Of 17 eyes, 11 (64.8%) had their original device in situ, 3 (17.6%) had their second device in situ, 1 (5.9%) had the device removed and replaced with a donor keratoplasty, and 2 (11.8%) were enucleated. At the last follow-up, 11 eyes (64.7%) were able to maintain improvement in vision, 5 (29.4%) had worsened vision, 1 (5.9%) had stable vision, and 9 (52.9%) had visual acuity

Alzheimer's Disease and Aging Association: Identification and Validation of Related Genes.

BACKGROUND: Aging is considered a key risk factor for Alzheimer's disease (AD). This study aimed to identify and validate potential aging-related genes associated with AD using bioinformatics analysis. METHODS: Datasets GSE36980 and GSE5281 were selected to screen differentially expressed genes (DEGs), and the immune cell correlation analysis and GSEA analysis of DEGs were performed. The intersection with senescence genes was taken as differentially expressed senescence-related genes (DESRGs), and the GSE44770 dataset was used for further validation. The potential biological functions and signaling pathways were determined by GO and KEGG, and the hub genes were identified by 12 algorithms in Cytohubba. The expression of 10 hub genes in different brain regions was determined and single-cell sequencing analysis was performed, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed. RESULTS: A total of 2137 DEGs were screened from the GSE36980 and GSE5281 datasets, and 278 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 29 DESRGs, including 14 senescence suppressor genes and 15 senescence inducible genes. The top 10 hub genes, including MDH1, CKB, PSMD14, SMARCA4, PEBP1, DDB2, ITPKB, ATF7IP, YAP1, and EWSR1 were screened. Furthermore, four diagnostic genes were identified: PMSD14, PEBP1, ITPKB, and ATF7IP. The ROC analysis showed that the respective area under the curves (AUCs) of PMSD14, PEBP1, ITPKB, and ATF7IP were 0.732, 0.701, 0.747, and 0.703 in the GSE36980 dataset and 0.870, 0.817, 0.902, and 0.834 in the GSE5281 dataset. In the GSE44770 dataset, PMSD14 (AUC, 0.838) and ITPKB (AUC, 0.952) had very high diagnostic values in the early stage of AD. Finally, based on these diagnostic genes, we found that the drug Abemaciclib is a targeted drug for the treatment of age-related AD. Flutamide can aggravate aging-related AD. CONCLUSION: The results of this study suggest that cellular SRGs might play an important role in AD. PMSD14, PEBP1, ITPKB, and ATF7IP have the potential as specific biomarkers for the early diagnosis of AD.

[Epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2018-2021].

Objective: To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. Methods: The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. Results: From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. Conclusion: From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

Autonomous artificial intelligence increases screening and follow-up for diabetic retinopathy in youth: the ACCESS randomized control trial.

Diabetic retinopathy can be prevented with screening and early detection. We hypothesized that autonomous artificial intelligence (AI) diabetic eye exams at the point-of-care would increase diabetic eye exam completion rates in a racially and ethnically diverse youth population. AI for Children's diabetiC Eye ExamS (NCT05131451) is a parallel randomized controlled trial that randomized youth (ages 8-21 years) with type 1 and type 2 diabetes to intervention (autonomous artificial intelligence diabetic eye exam at the point of care), or control (scripted eye care provider referral and education) in an academic pediatric diabetes center. The primary outcome was diabetic eye exam completion rate within 6 months. The secondary outcome was the proportion of participants who completed follow-through with an eye care provider if deemed appropriate. Diabetic eye exam completion rate was significantly higher (100%, 95%CI: 95.5%, 100%) in the intervention group (n = 81) than the control group (n = 83) (22%, 95%CI: 14.2%, 32.4%)(p < 0.001). In the intervention arm, 25/81 participants had an abnormal result, of whom 64% (16/25) completed follow-through with an eye care provider, compared to 22% in the control arm (p < 0.001). Autonomous AI increases diabetic eye exam completion rates in youth with diabetes.