[A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer].

Objective: To explore the value of cervical cytologic DNA methylation for screening cervical cancer. Methods: This study was a prospective multicenter study conducted from May to October 2022 in Peking Union Medical College Hospital, Zhejiang Provincial People's Hospital, and the Second Affiliated Hospital of Zhejiang University School of Medicine. Women who accepted opportunistic cervical cancer screening in gynecological outpatient clinics were subjected to liquid-based thin-layer cytology testing (TCT), high-risk human papillomavirus (hrHPV) DNA testing and PAX1/JAM3 dual-genes methylation testing (PAX1m/JAM3m). Colposcopy evaluation and biopsy were offered to women according to current guidelines. The accuracies of various testing methods and their combinations were compared based on histological diagnosis. Results: A total of 1 184 samples diagnosed by histopathology were included in this study, consisting of 541 cases (45.7%) of benign cervical tissue or chronic cervicitis, 273 (23.1%) of cervical intraepithelial neoplasia (CIN) 1, 168 (14.2%) of CIN2, 140 (11.8%) of CIN3, and 62 (5.2%) of cervical cancer. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN2 or more severe lesions (CIN2+) were 74.1% and 95.9%, respectively. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN3+were 87.6% and 86.8%, respectively. Receiver operating characteristic curve analysis showed that, for detecting CIN3+, the area under curve of PAX1m/JAM3m testing (0.872, 95%CI: 0.847-0.897) was significantly superior to TCT testing (0.580, 95%CI: 0.551-0.610) or hrHPV testing (0.503, 95%CI: 0.479-0.515) (all P values<0.05). Conclusions: The PAX1m/JAM3m test in cervical exfoliated cells has excellent accuracy for the diagnosis of both CIN2+and CIN3+, which is superior to traditional screening protocols and screening strategies.

ATS core curriculum 2023. Pediatric pulmonary medicine: Respiratory disorders in infants.

The American Thoracic Society Core Curriculum updates clinicians annually in pediatric pulmonary disease. This is a summary of the Pediatric Pulmonary Medicine Core Curriculum presented at the 2023 American Thoracic Society International Conference. The respiratory disorders of infancy discussed in this year's review include: the care of the patient with bronchopulmonary dysplasia in the neonatal intensive care unit, clinical phenotypes and comorbidities; diffuse lung disease; pulmonary hypertension; central and obstructive sleep apnea. The care of infants with respiratory disorders often poses significant challenges to the general pediatric pulmonologist, sleep clinician, and neonatologist. This review aims to highlight the most clinically relevant aspects of the evaluation, management, and outcomes of infants with these key respiratory disorders, while emphasizing the importance of multidisciplinary care. Furthermore, this document summarizes essential aspects of genetic testing, novel imaging and treatment modalities, and includes multiple resources for clinical practice.

[Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism].

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

[Research on the formulation and revision of standard limits for antimony,boron and vanadium in the "Standards for Drinking Water Quality (GB5749-2022)" in China].

China is rich in antimony, boron, and vanadium mineral resources, which have been detected in environmental water bodies and drinking water. During the revision process of the "Standards for Drinking Water Quality (GB5749-2006)", research and evaluation are focused on three indicators: antimony, boron and vanadium. Vanadium is added and the limit value of boron is adjusted. This study reviews and discusses the technical contents related to the revision of the antimony, boron and vanadium, including the environmental presence levels, exposure status, health effects, and the revision of the standard limits of these three indicators. Suggestions are also made for the implementation of this standard.

ATS Core Curriculum 2022. Pediatric Pulmonary Medicine: Updates in pediatric neuromuscular disease.

The American Thoracic Society Core Curriculum updates clinicians annually in pediatric pulmonary disease. This is a concise review of the Pediatric Pulmonary Medicine Core Curriculum presented at the 2022 American Thoracic Society International Conference. Neuromuscular diseases (NMD) comprise a variety of conditions that commonly affect the respiratory system and cause significant morbidity including dysphagia, chronic respiratory failure, and sleep disordered breathing. Respiratory failure is the most common cause of mortality in this population. Substantial progress has been made in diagnosis, monitoring and treatment for NMD over the last decade. Pulmonary function testing (PFT) is utilized to objectively measure respiratory pump function and PFT milestones are utilized in NMD-specific pulmonary care guidelines. New disease modifying therapies are approved for the treatment of patients with Duchenne muscular dystrophy and spinal muscular atrophy (SMA), including the first ever approved systemic gene therapy, in the case of SMA. Despite extraordinary progress in the medical management of NMD, little is known regarding the respiratory implications and long-term outcomes for patients in the era of advanced therapeutics and precision medicine. The combination of technological and biomedical advancements has increased the complexity of the medical decision-making process for patients and families, thus emphasizing the importance of balancing respect for autonomy with the other foundational principles of medical ethics. This review features an overview of PFT, noninvasive ventilation strategies, novel and developing therapies, as well as the ethical considerations specific to the management of patients with pediatric NMD.

[Effects of surgical procedures and general anesthesia exposure within 2 hours in early childhood on neurodevelopmental outcomes in school-age].

Objective: To observe the effect of surgical procedures and general anesthesia exposure (<2 h) in early childhood on neurodevelopmental outcomes in school-age. Methods: A total of 147 children aged 6-12 years old, who received surgery under general anesthesia (<2 h) at the age of 0-2 years in Children's Hospital of Nanjing Medical Universityfrom June 2009 to December 2012 were retrospectively enrolled in this study (from June 2018 to December 2021) as exposure group, including 76 males and 71 females, with a mean age of (8.8±1.6) years. All the cases were divided into single-exposure group (n=65) and multiple-exposure group (≥2 times, n=82) according to different times of anesthesia exposure. According to the cohort of exposure group, 160 healthy children of the same age with no history of surgery under general anesthesia were recruited from the community from June 2018 to December 2021 as the control group, including 87 males and 73 females, and aged (8.6±1.9) years. A variety of standardized neurological tests including Wechsler intelligence scale for children fourth edition (WSC-Ⅳ), integrated visual and auditory continuous performance test (IVA-CPT), Swanson Nolan and Pelham, version Ⅳ (SNAP-Ⅳ), children sensory integration capacity development rating scale (CSIC), and social living ability scale were performed in all subjects by a child health specialist who failed to know the details. The primary outcome was the full-scale IQ (FSIQ) in WISC-Ⅳ, and the secondary outcomes were IVA-CPT, SNAP-Ⅳ, CSIC, and social living ability scale. Results: The FSIQ of single-exposure, multiple-exposure and control groups was 105.4±14.1, 100.9±10.2 and 103.6±13.5, respectively, with no statistically significant difference (F=2.37, P=0.095). The FSIQ of different first age exposure groups (aged 0-6 months, 7-12 months and 1-2 years) was 99.8±10.2, 104.5±10.5 and 104.4±14.5, respectively, with no statistically significant difference (F=2.39, P=0.095). The FSIQ of different exposure duration groups (0-59 min, 60-119 min and control group) was 102.8±11.3, 103.0±13.7 and 103.6±13.5, respectively, with no statistically significant difference (F=0.13, P=0.882). As for the secondary outcomes, the scores of visual persistence quotient in single-exposure, multiple-exposure and control groups were 94.8±10.5, 94.0±10.9 and 100.6±17.7, with a statistically significant difference (F=6.96, P=0.001). In terms of locomotion in social living ability scale, the score of the three groups was 10.0±0.2, 10.2±0.6 and 10.4±0.7, respectively, with a statistically significant difference (F=10.61, P<0.001), but all were within the standard range. Conclusions: The surgical procedures and general anesthesia exposure within 2 hours in early childhood has no effect on the overall FSIQ in school age, but has a slight impacts on the visual persistence quotient of IVA-CPT and the locomotion score of social living ability scale.

[Comparison of time series and case-crossover analyses in environmental epidemiology].

Time-series and case-crossover are two main study designs in environmental epidemiology. However, due to the differences in design principles and model construction between the two analyses, the results of the two analyses may not be consistent. Herein, we examined the short-term effect of cold spells on cardiovascular mortality in Nanjing using both time series and case-crossover analyses, aiming to provide a basis for the selection of appropriate research design in environmental epidemiology.

The cross-sectional study of depressive symptoms and associated factors among adolescents by backpropagation neural network.

OBJECTIVES: This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents. STUDY DESIGN: Cross-sectional study. METHODS: Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11-19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms. RESULTS: The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%). CONCLUSION: Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms.

ATS Core Curriculum 2021. Pediatric Pulmonary Medicine: Pulmonary Infections.

The following is a concise review of the Pediatric Pulmonary Medicine Core reviewing pediatric pulmonary infections, diagnostic assays, and imaging techniques presented at the 2021 American Thoracic Society Core Curriculum. Molecular methods have revolutionized microbiology. We highlight the need to collect appropriate samples for detection of specific pathogens or for panels and understand the limitations of the assays. Considerable progress has been made in imaging modalities for detecting pediatric pulmonary infections. Specifically, lung ultrasound and lung magnetic resonance imaging are promising radiation-free diagnostic tools, with results comparable with their radiation-exposing counterparts, for the evaluation and management of pulmonary infections. Clinicians caring for children with pulmonary disease should ensure that patients at risk for nontuberculous mycobacteria disease are identified and receive appropriate nontuberculous mycobacteria screening, monitoring, and treatment. Children with coronavirus disease (COVID-19) typically present with mild symptoms, but some may develop severe disease. Treatment is mainly supportive care, and most patients make a full recovery. Anticipatory guidance and appropriate counseling from pediatricians on social distancing and diagnostic testing remain vital to curbing the pandemic. The pediatric immunocompromised patient is at risk for invasive and opportunistic pulmonary infections. Prompt recognition of predisposing risk factors, combined with knowledge of clinical characteristics of microbial pathogens, can assist in the diagnosis and treatment of specific bacterial, viral, or fungal diseases.

[Therapeutic effect of tonsillectomy on IgA nephropathy after kidney transplantation].

Objective: To observe the clinical effect of tonsillectomy on IgA nephropathy (IgAN) after renal transplantation. Methods: From March 2011 to July 2018, 201 kidney transplantation recipients who were diagnosed of IgAN by transplant renal biopsy in the Department of Organ Transplantation of the First Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed, of which 18 patients underwent tonsillectomy after renal biopsy. The clinical data of the 18 patients were collected, patient and kidney survival time and function of the transplanted kidney were analyzed. Results: Of the 18 recipients, 13 were male and 5 were female, with an average age of (36.0±10.9) years. All 18 patients survived during follow-up. Two patients returned to dialysis treatment 10 months and 14 months after tonsillectomy, respectively. The creatinine was 94 (78, 133) µmol/L, 95 (74, 139) µmol/L, 106 (87, 158) µmol/L and 95(81, 147) µmol/L before tonsillectomy, 3 months, 1 year and 2 years after tonsillectomy, respectively (P=0.206). Urinary protein quantification was 0.31 (0.16, 1.38) g/24 h, 0.34 (0.10, 1.42) g/24 h, 0.33 (0.11, 0.56) g/24 h and 0.25 (0.10, 0.50) g/24 h at the same time points, respectively (P=0.104). The two patients who returned to dialysis were diagnosed of IgAN by transplant renal biopsy because of elevated creatinine, proteinuria and hematuria, 9 years and 4 years after kidney transplant respectively. Renal biopsy suggested that glomerular and segmental sclerosis were 7/24, 5/24 and 1/6, 2/6, respectively. Additionally, interstitial fibrosis and tubular atrophy (IF/TA) were both occupied 30% in the biopsies, and tonsillectomy was performed 461 days and 1 077 days after diagnosis of IgAN, respectively. Conclusions: Tonsillectomy can maintain the stability of renal function and prevent the aggravation of proteinuria in IgAN patients after renal transplantation. However, if pathology suggests obvious glomerulosclerosis or IF/TA, tonsillectomy may not be effective.

LINC00460 promotes proliferation and inhibits apoptosis of non-small cell lung cancer cells through targeted regulation of miR-539.

OBJECTIVE: To explore the effects of long intergenic non-coding ribonucleic acid 00460 (LINC00460) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: In this study, the expression of LINC00460 in lung cancer tissues and its prognostic potential in NSCLC patients were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) website and the Cancer Genome Atlas (TCGA) database. Then, the influences of silenced LINC00460 on proliferation and apoptosis in A549 cells were observed via methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and flow cytometry in vitro. Moreover, Dual-Luciferase reporter assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the targeting relationship between LINC00460 and micro RNA (miR)-539. The biological role of the LINC00460/miR-539 axis in the proliferation of A549 cells was examined using MTT assay. RESULTS: It was found that the expression level of LINC00460 was significantly upregulated in NSCLC tissues and cell lines, and particularly negatively correlated with the overall survival (OS). According to the in vitro experimental results, LINC00460 knockdown inhibited the proliferation of A549 cells, but promoted their apoptosis. Dual-Luciferase reporter assay results revealed that miR-539 was directly targeted by LINC00460 and involved in the LINC00460-mediated proliferation of A549 cells. CONCLUSIONS: LINC00460 is overexpressed in NSCLC tissues and can promote the growth of NSCLC cells by targeting miR-539.

microRNA-23B inhibits non-small cell lung cancer proliferation, invasion and migration via downregulation of RUNX2 and inhibition of Wnt/Β-catenin signaling pathway.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. MicroRNAs (miRNAs/miRs) have been reported to play significant roles in the progression of human tumors, however, the expression and biological role of miR-23b in NSCLC remains elusive. Underexpression of miR-23b was detected in NSCLC tissues in comparison with the matched para-carcinoma tissues. The clinical value of miR-23b was analyzed, and the findings showed that miR-23b expression was negatively correlated with poor overall survival and malignant clinicopathologic characteristics of NSCLC patients. Furthermore, functional assays demonstrated that overexpression of miR-23b inhibited NSCLC cell viability, invasion and migration. Luciferase reporter assay and qRT-PCR revealed that RUNX2 was a functional target of miR-23b. The elevated expression of RUNX2 was positively correlated with overall survival of NSCLC patients. Additionally, Western blot analysis indicated that EMT and Wnt/ß-catenin pathways were blocked by the upregulation of miR-23b. Taken together, these data demonstrated that dysregulation of miR-23b/RUNX2 signal may be a novel therapeutic target for the treatment of NSCLC.

MiR-20a promotes lung tumorigenesis by targeting RUNX3 via TGF-ß signaling pathway.

MiR-20a shows a significant role in the development of various human tumors. However, its specific biological function in non-small-cell lung cancer (NSCLC) is still not clear. qRT-PCR was applied for detecting miR-20a expression. The analysis of cell growth and apoptosis were performed by MTT, xenograft models, Western blot assays. Dual luciferase reporter, Western blotting and qRT-PCR were carried out to verify the potential target of miR-20a. In NSCLC tissues and cells, miR-20a was highly expressed and RUNX3 was lowly expressed. Moreover, up-regulation of miR-20a expression promoted NSCLC cell proliferation, invasion and migration, while low-expression of miR-20a showed the converse case on cell proliferation, invasion and migration. RUNX3 was verified as the direct target of miR-20a and it could overturn its biological function in NSCLC cells. Moreover, miR-20a negatively regulated RUNX3 expression. Mechanistically, increasing miR-20a expression inhibited RUNX3 expression and then activated the TGF-ß signaling pathway. Taken together, our results demonstrated that re-expression of miR-20a promoted lung tumorigenesis by down-regulation of RUNX3 and facilitating the activation of TGF-ß signaling pathway.

ATS Core Curriculum 2020. Pediatric Pulmonary Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the pediatric pulmonary medicine core, including pediatric hypoxemic respiratory failure; modalities in noninvasive management of chronic respiratory failure in childhood; surgical and nonsurgical management of congenital lung malformations; an update on smoke inhalation lung injury; an update on vaporizers, e-cigarettes, and other electronic delivery systems; pulmonary complications of sarcoidosis; pulmonary complications of congenital heart disease; and updates on the management of congenital diaphragmatic hernia.

Constraining the Spin-Dependent WIMP-Nucleon Cross Sections with XENON1T.

We report the first experimental results on spin-dependent elastic weakly interacting massive particle (WIMP) nucleon scattering from the XENON1T dark matter search experiment. The analysis uses the full ton year exposure of XENON1T to constrain the spin-dependent proton-only and neutron-only cases. No significant signal excess is observed, and a profile likelihood ratio analysis is used to set exclusion limits on the WIMP-nucleon interactions. This includes the most stringent constraint to date on the WIMP-neutron cross section, with a minimum of 6.3×10^{-42} cm^{2} at 30 GeV/c^{2} and 90% confidence level. The results are compared with those from collider searches and used to exclude new parameter space in an isoscalar theory with an axial-vector mediator.

First Results on the Scalar WIMP-Pion Coupling, Using the XENON1T Experiment.

We present first results on the scalar coupling of weakly interacting massive particles (WIMPs) to pions from 1 t yr of exposure with the XENON1T experiment. This interaction is generated when the WIMP couples to a virtual pion exchanged between the nucleons in a nucleus. In contrast to most nonrelativistic operators, these pion-exchange currents can be coherently enhanced by the total number of nucleons and therefore may dominate in scenarios where spin-independent WIMP-nucleon interactions are suppressed. Moreover, for natural values of the couplings, they dominate over the spin-dependent channel due to their coherence in the nucleus. Using the signal model of this new WIMP-pion channel, no significant excess is found, leading to an upper limit cross section of 6.4×10^{-46} cm^{2} (90% confidence level) at 30 GeV/c^{2} WIMP mass.

Light Dark Matter Search with Ionization Signals in XENON1T.

We report constraints on light dark matter (DM) models using ionization signals in the XENON1T experiment. We mitigate backgrounds with strong event selections, rather than requiring a scintillation signal, leaving an effective exposure of (22±3) tonne day. Above ∼0.4 keV_{ee}, we observe <1 event/(tonne day keV_{ee}), which is more than 1000 times lower than in similar searches with other detectors. Despite observing a higher rate at lower energies, no DM or CEvNS detection may be claimed because we cannot model all of our backgrounds. We thus exclude new regions in the parameter spaces for DM-nucleus scattering for DM masses m_{χ} within 3-6 GeV/c^{2}, DM-electron scattering for m_{χ}>30 MeV/c^{2}, and absorption of dark photons and axionlike particles for m_{χ} within 0.186-1 keV/c^{2}.

Search for Light Dark Matter Interactions Enhanced by the Migdal Effect or Bremsstrahlung in XENON1T.

Direct dark matter detection experiments based on a liquid xenon target are leading the search for dark matter particles with masses above ∼5 GeV/c^{2}, but have limited sensitivity to lighter masses because of the small momentum transfer in dark matter-nucleus elastic scattering. However, there is an irreducible contribution from inelastic processes accompanying the elastic scattering, which leads to the excitation and ionization of the recoiling atom (the Migdal effect) or the emission of a bremsstrahlung photon. In this Letter, we report on a probe of low-mass dark matter with masses down to about 85 MeV/c^{2} by looking for electronic recoils induced by the Migdal effect and bremsstrahlung using data from the XENON1T experiment. Besides the approach of detecting both scintillation and ionization signals, we exploit an approach that uses ionization signals only, which allows for a lower detection threshold. This analysis significantly enhances the sensitivity of XENON1T to light dark matter previously beyond its reach.

Sequential releasing of VEGF and BMP-2 in hydroxyapatite collagen scaffolds for bone tissue engineering: Design and characterization.

The property of biomaterials to control the sequential release of growth factors has been widely concerned in the field of bone repair and regeneration. Double-factor sustained-release scaffolds have good biocompatibility and bioactivity. O­Carboxymethyl chitosan microspheres (O-CMCS) has antimicrobial activity, biodegradability, biocompatibility and film formation. This study developed scaffolds materials with microspheres with a purpose of forming a controlled slow release secondary structure. O-CMCS were used as drug carrier to construct the compound sustained-release system with rhBMP-2 and VEGF double factors release. The O-CMCS were loaded with rhBMP-2 and the hydroxyapatite collagen (HC) scaffolds were loaded with VEGF to prepare the scaffolds. These were double factors composite sustained-release system scaffolds. The biocompatibility of the sustained-release system was evaluated by in vitro and in vivo experiments. HC composite scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction detection (XRD), in vitro sustained release test, in vitro cell culture and in vivo animal experiments. The results showed that rhBMP-2/VEGF in HC composite scaffolds (HCBV) successfully achieved the sequential release of the double factors, which could benefit bone regeneration.