Mono- and biallelic variant effects on disease at biobank scale.

Identifying causal factors for Mendelian and common diseases is an ongoing challenge in medical genetics1. Population bottleneck events, such as those that occurred in the history of the Finnish population, enrich some homozygous variants to higher frequencies, which facilitates the identification of variants that cause diseases with recessive inheritance2,3. Here we examine the homozygous and heterozygous effects of 44,370 coding variants on 2,444 disease phenotypes using data from the nationwide electronic health records of 176,899 Finnish individuals. We find associations for homozygous genotypes across a broad spectrum of phenotypes, including known associations with retinal dystrophy and novel associations with adult-onset cataract and female infertility. Of the recessive disease associations that we identify, 13 out of 20 would have been missed by the additive model that is typically used in genome-wide association studies. We use these results to find many known Mendelian variants whose inheritance cannot be adequately described by a conventional definition of dominant or recessive. In particular, we find variants that are known to cause diseases with recessive inheritance with significant heterozygous phenotypic effects. Similarly, we find presumed benign variants with disease effects. Our results show how biobanks, particularly in founder populations, can broaden our understanding of complex dosage effects of Mendelian variants on disease.

Strain-hardening and suppression of shear-banding in rejuvenated bulk metallic glass.

Strain-hardening (the increase of flow stress with plastic strain) is the most important phenomenon in the mechanical behaviour of engineering alloys because it ensures that flow is delocalized, enhances tensile ductility and inhibits catastrophic mechanical failure1,2. Metallic glasses (MGs) lack the crystallinity of conventional engineering alloys, and some of their properties-such as higher yield stress and elastic strain limit3-are greatly improved relative to their crystalline counterparts. MGs can have high fracture toughness and have the highest known 'damage tolerance' (defined as the product of yield stress and fracture toughness)4 among all structural materials. However, the use of MGs in structural applications is largely limited by the fact that they show strain-softening instead of strain-hardening; this leads to extreme localization of plastic flow in shear bands, and is associated with early catastrophic failure in tension. Although rejuvenation of an MG (raising its energy to values that are typical of glass formation at a higher cooling rate) lowers its yield stress, which might enable strain-hardening5, it is unclear whether sufficient rejuvenation can be achieved in bulk samples while retaining their glassy structure. Here we show that plastic deformation under triaxial compression at room temperature can rejuvenate bulk MG samples sufficiently to enable strain-hardening through a mechanism that has not been previously observed in the metallic state. This transformed behaviour suppresses shear-banding in bulk samples in normal uniaxial (tensile or compressive) tests, prevents catastrophic failure and leads to higher ultimate flow stress. The rejuvenated MGs are stable at room temperature and show exceptionally efficient strain-hardening, greatly increasing their potential use in structural applications.

New radiofrequency ablation procedure for selective reduction in complicated monochorionic twin or triplet pregnancy using multistep, incremental expansion technique.

OBJECTIVE: Radiofrequency ablation (RFA) is the preferred approach for selective reduction in complex monochorionic (MC) multiple pregnancies owing to the ease of operation and minimal invasiveness. To optimize the RFA technique and reduce the risk of adverse pregnancy outcome resulting from the heat-sink effect of RFA therapy, we used an innovative RFA method, in which an electrode needle was expanded incrementally and stepwise. This study aimed to assess the efficacy and safety profile of this novel multistep incremental expansion RFA method for selective fetal reduction in MC twin and triplet pregnancies. METHODS: This was a single-center retrospective cohort study of all MC multiple pregnancies undergoing RFA between March 2016 and October 2022 at our center. The multistep RFA technique involved the use of an expandable needle, which was gradually expanded during the RFA procedure until cessation of umbilical cord blood flow was achieved. The needle used for the single-step RFA method was fully extended from the start of treatment. RESULTS: In total, 132 MC multiple pregnancies underwent selective reduction using RFA, including 50 cases undergoing multistep RFA and 82 cases undergoing single-step RFA. The overall survival rates were not significantly different between the multistep and single-step RFA groups (81.1% vs 72.3%; P = 0.234). Similarly, the rates of preterm prelabor rupture of the membranes within 2 weeks after RFA, procedure-related complications, spontaneous preterm delivery and pathological findings on cranial ultrasound, as well as gestational age at delivery and birth weight, did not differ between the two groups. However, there was a trend towards a prolonged procedure-to-delivery interval following multistep RFA compared with single-step RFA (median, 109 vs 99 days; P = 0.377). Moreover, the fetal loss rate within 2 weeks after RFA in the multistep RFA group was significantly lower than that in the single-step RFA group (10.0% vs 24.4%; P = 0.041). The median ablation time was shorter (5.3 vs 7.8 min; P < 0.001) and the median ablation energy was lower (10.2 vs 18.0 kJ; P < 0.001) in multistep compared with single-step RFA. There were no significant differences in neonatal outcomes following multistep vs single-step RFA. CONCLUSIONS: Overall survival rates were similar between the two RFA methods. However, the multistep RFA technique was associated with a lower risk of fetal loss within 2 weeks after RFA. The multistep RFA technique required significantly less ablation energy and a shorter ablation time compared with single-step RFA in selective fetal reduction of MC twin and triplet pregnancies. Additionally, there was a trend towards a prolonged procedure-to-delivery interval with the multistep RFA technique. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Transarterial chemoembolization combined with microwave ablation versus repeated resection for recurrent small hepatocellular carcinoma after resection: What is the better treatment?

PURPOSE: This study aimed to compare the effectiveness of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) versus repeated hepatic resection (RHR) in patients with recurrent small hepatocellular carcinoma (sHCC) following primary resection. MATERIALS AND METHODS: A total of 59 patients diagnosed with recurrent sHCC (≤3 cm) and treated with either TACE-MWA or RHR were recruited from two centers between June 2015 and October 2021. Patients were matched using propensity scores at a 1:1 ratio. Disease-free survival (DFS), overall survival (OS), and complications were assessed and compared between the two treatment groups. RESULTS: After propensity score matching, 38 patients were included, with 19 in each group. Prior to matching, the 1-, 3-, and 5-year DFS rates for the TACE-MWA group were 68.1%, 46.6%, and 23.3%, respectively, and for the RHR group, they were 84.6%, 47.3%, and 47.3%, respectively. The corresponding 1-, 3-, and 5-year OS rates for TACE-MWA were 100.0%, 83.7%, and 47.8%, while for RHR, they were 100.0%, 95.0%, and 45.2%. After matching, the 1-, 3-, and 5-year DFS rates were 78.0%, 48.3%, and 24.1% for TACE-MWA, and 77.5%, 38.7%, and 38.7% for RHR. The 1-, 3-, and 5-year OS rates for TACE-MWA were 100.0%, 88.9%, and 54.9%, and for RHR, they were 100.0%, 93.3%, and 44.4%. Statistical analysis showed no significant differences in DFS rates (P=0.834 before matching, P=0.490 after matching) or OS rates (P=0.825 before matching, P=0.625 after matching) between the two groups. CONCLUSIONS: TACE-MWA demonstrates comparable effectiveness to RHR in managing recurrent sHCC.

Regional variations in retinopathy of prematurity incidence for preterm infants <32 weeks' gestation in China.

OBJECTIVES: National-level data on the incidence of retinopathy of prematurity (ROP) in different regions of China is insufficient. This study aimed to compare ROP incidences and care practices in different regions of China and their relationship with regional gross domestic product (GDP) per capita. STUDY DESIGN: Retrospective cohort study. METHODS: All infants born at <32 weeks gestational age (GA) and admitted to 70 neonatal intensive care units (NICUs) from January 1, 2019, to December 31, 2020, were enrolled. Hospitals were categorised into three regional groups according to geographical locations and GDP per capita from high to low: Eastern, Central, and Western China. The incidence of death or ROP, and care practices were compared among the groups. RESULTS: A total of 18,579 infants were enrolled. Median GA was 29.9 (interquartile range 28.4-31.0) weeks and birth weight was 1318.1 (317.2) g. The percentage of GA <28 weeks, complete administration of antenatal steroids, and weight gain velocity during NICU stay were highest in Eastern China and lowest in Western China (all P < 0.01). In Eastern, Central, and Western China, the rates of death or any stage of ROP were 33.3%, 38.5%, and 39.2%, respectively (P < 0.01). CONCLUSIONS: There were considerable regional disparities in ROP incidence in preterm infants with GA <32 weeks in China. The incidence of death or ROP ranged from high to low in Western, Central, and Eastern China.

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

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

Predictive model for postoperative unrecovered olfactory function in CRSwNP patients with olfactory disorder.

BACKGROUND: Olfactory disorder (OD) is a prevalent and challenging symptom in chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to investigate the risk factors and develop a predictive model for poor olfactory prognosis in CRSwNP patients with OD after endoscopic sinus surgery (ESS). METHOD: Seventy-eight CRSwNP patients with OD who underwent ESS were enrolled. Preoperative and 6-month-postoperative olfactory function were assessed using Sniffin' Sticks. Receiver operating characteristics (ROC) curves were constructed to set the cutoff points. Risk factors were determined by logistic models. A power analysis was conducted to evaluate the sample size. RESULTS: Overall, 66.7% of CRSwNP patients had unrecovered olfaction after surgery. Patients with unrecovered olfaction displayed higher preoperative threshold-discrimination-identification (TDI) score, lower Questionnaire for Olfactory Disorders-Negative Statements (QOD-NS) score, lower total olfactory cleft score (TOCS), and fewer tissue eosinophils than those of the improved/recovered group. QOD-NS≤5.0, preoperative TOCS≤4.5 and tissue eosinophil count≤8.3 were independent risk factors for unrecovered olfaction. Based on these variables, a predictive model was developed. The area under the ROC curve for the model was 0.845, and the optimal cutoff value was 2.0 points, with a sensitivity of 82.7% and specificity of 80.8%. CONCLUSIONS: Low levels of QOD-NS score (preoperative), TOCS (preoperative) and tissue eosinophil count are independent risk factors for short-term unrecovered olfaction in CRS patients with OD postoperatively. The predictive model developed here is practical and convenient for the early identification of poor prognosis of OD, enabling early additional intervention.

[Analysis of the accuracy between orthopedic robot-assisted and traditional manual pedicle screw placement techniques in adult degenerative scoliosis posterior surgery].

Objective: To comparing the accuracy of pedicle screw placement in posterior surgery for adult degenerative scoliosis (ADS) between robotic-assisted and traditional freehand techniques. Methods: This retrospective study included 92 patients with ADS who underwent posterior spinal surgery at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) between March 2019 and December 2023. There were 19 males and 73 females with a mean age of (63.6±9.8) years. The patients were divided into two groups based on the technique used for pedicle screw placement: robot-assisted group (34 cases) and manual group (58 cases). Operative duration, intraoperative blood loss, facet joint violation, postoperative complications, magnitude of curve correction, visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 1 week postoperatively, and 1 month postoperatively were compared and analyzed between the two groups. The Gertzbein-Robbins classification criteria was used to assess the accuracy of screw placement. Results: Differences in baseline data, operative duration, intraoperative blood loss, magnitude of curve correction, and VAS and ODI scores preoperatively, 1 week postoperatively, and 1 month postoperatively between the two groups exhibited no statistically significant differences (all P>0.05). The accuracy of pedicle screw placement in the robot-assisted group was significantly higher than that in the manual group [90.9% (416/458) vs 80.1% (697/870), P<0.001]. In terms of surgical segments, in T1-T12 and L1-S1 segments, the accuracy of pedicle screw placement in the robot group were both significantly higher than those in the control group [91.5% (130/142) vs 77.8% (186/239), P=0.001; 90.3% (271/300) vs 80.8% (502/621), P<0.001]. However, no significant differences was observed in the accuracy of S2-alar-iliac (S2AI) screw placement between the two groups [90.0%(9/10) vs 93.8%(15/16), P=0.727]. Moreover, no significant differences was found in the deviation direction of the cortical screw penetration between both groups (P=0.133). Significant differences were observed in the accuracy of screw placement between the Nash Moe 2 and 3 vertebral bodies in the robot group compared with those in the control group [88.9% (88/99) vs 71.0% (115/162), P=0.001; 89.2% (83/93) vs 60.2% (68/113), P<0.001]. Additionally, the incidence and grade of facet joint violation in the manual group were both significantly higher than those in the robot-assisted group (both P<0.001). No statistically significant differences was identified in postoperative complications between the two groups (P=0.841). Conclusion: It suggests that robot-assisted pedicle screw placement in posterior surgery for patients with ADS can significantly improve the accuracy of screw placement and reduce the incidence of facet joint violation.

[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Emphasizing the timing and procedure selection for vitrectomy in pathological myopic traction maculopathy].

Myopic maculopathy is the primary cause of irreversible visual impairment in patients with pathologic myopia, and myopic traction maculopathy often requires vitrectomy for treatment. Myopic traction maculopathy encompasses epiretinal membrane, foveoschisis, macular hole, and macular hole-related retinal detachment. It is recommended to perform vitrectomy combined with inner limiting membrane peeling for Type II epiretinal membrane, foveal-sparing inner limiting membrane peeling for foveoschisis, inverted inner limiting membrane flap technique for macular hole, and vitrectomy combined with macular buckle for refractory macular hole-related retinal detachment. Myopic traction maculopathy is a chronically progressive condition, and surgeons need to accurately determine the timing of surgery and choose appropriate procedures to maximize the benefits for patients.

[Preliminary study on automatic quantification and grading of leopard spots fundus based on deep learning technology].

Objective: To achieve automatic segmentation, quantification, and grading of different regions of leopard spots fundus (FT) using deep learning technology. The analysis includes exploring the correlation between novel quantitative indicators, leopard spot fundus grades, and various systemic and ocular parameters. Methods: This was a cross-sectional study. The data were sourced from the Beijing Eye Study, a population-based longitudinal study. In 2001, a group of individuals aged 40 and above were surveyed in five urban communities in Haidian District and three rural communities in Daxing District of Beijing. A follow-up was conducted in 2011. This study included individuals aged 50 and above who participated in the second 5-year follow-up in 2011, considering only the data from the right eye. Color fundus images centered on the macula of the right eye were input into the leopard spot segmentation model and macular detection network. Using the macular center as the origin, with inner circle diameters of 1 mm, 3 mm, and outer circle diameter of 6 mm, fine segmentation of the fundus was achieved. This allowed the calculation of the leopard spot density (FTD) and leopard spot grade for each region. Further analyses of the differences in ocular and systemic parameters among different regions' FTD and leopard spot grades were conducted. The participants were categorized into three refractive types based on equivalent spherical power (SE): myopia (SE<-0.25 D), emmetropia (-0.25 D≤SE≤0.25 D), and hyperopia (SE>0.25 D). Based on axial length, the participants were divided into groups with axial length<24 mm, 24-26 mm, and>26 mm for the analysis of different types of FTD. Statistical analyses were performed using one-way analysis of variance, Kruskal-Wallis test, Bonferroni test, and Spearman correlation analysis. Results: The study included 3 369 participants (3 369 eyes) with an average age of (63.9±10.6) years; among them, 1 886 were female (56.0%) and 1, 483 were male (64.0%). The overall FTD for all eyes was 0.060 (0.016, 0.163); inner circle FTD was 0.000 (0.000, 0.025); middle circle FTD was 0.030 (0.000, 0.130); outer circle FTD was 0.055 (0.009, 0.171). The results of the univariate analysis indicated that FTD in various regions was correlated with axial length (overall: r=0.38, P<0.001; inner circle: r=0.31, P<0.001; middle circle: r=0.36, P<0.001; outer circle: r=0.39, P<0.001), subfoveal choroidal thickness (SFCT) (overall: r=-0.69, P<0.001; inner circle: r=-0.57, P<0.001; middle circle: r=-0.68, P<0.001; outer circle: r=-0.72, P<0.001), age (overall: r=0.34, P<0.001; inner circle: r=0.30, P<0.001; middle circle: r=0.31, P<0.001; outer circle: r=0.35, P<0.001), gender (overall: r=-0.11, P<0.001; inner circle: r=-0.04, P<0.001; middle circle: r=-0.07, P<0.001; outer circle: r=-0.11, P<0.001), SE (overall: r=-0.20; P<0.001; inner circle: r=-0.19, P<0.001; middle circle: r=-0.20, P<0.001; outer circle: r=-0.20, P<0.001), uncorrected visual acuity (overall: r=-0.18, P<0.001; inner circle: r=-0.26, P<0.001; middle circle: r=-0.24, P<0.001; outer circle: r=-0.22, P<0.001), and body mass index (BMI) (overall: r=-0.11, P<0.001; inner circle: r=-0.13, P<0.001; middle circle: r=-0.14, P<0.001; outer circle: r=-0.13, P<0.001). Further multivariate analysis results indicated that different region FTD was correlated with axial length (overall: ß=0.020, P<0.001; inner circle: ß=-0.022, P<0.001; middle circle: ß=0.027, P<0.001; outer circle: ß=0.022, P<0.001), SFCT (overall: ß=-0.001, P<0.001; inner circle: ß=-0.001, P<0.001; middle circle: ß=-0.001, P<0.001; outer circle: ß=-0.001, P<0.001), and age (overall: ß=0.002, P<0.001; inner circle: ß=0.001, P<0.001; middle circle: ß=0.002, P<0.001; outer circle: ß=0.002, P<0.001). The distribution of overall (H=56.76, P<0.001), inner circle (H=72.22, P<0.001), middle circle (H=75.83, P<0.001), and outer circle (H=70.34, P<0.001) FTD differed significantly among different refractive types. The distribution of overall (H=373.15, P<0.001), inner circle (H=367.67, P<0.001), middle circle (H=389.14, P<0.001), and outer circle (H=386.89, P<0.001) FTD differed significantly among different axial length groups. Furthermore, comparing various levels of FTD with systemic and ocular parameters, significant differences were found in axial length (F=142.85, P<0.001) and SFCT (F=530.46, P<0.001). Conclusions: The use of deep learning technology enables automatic segmentation and quantification of different regions of theFT, as well as preliminary grading. Different region FTD is significantly correlated with axial length, SFCT, and age. Individuals with older age, myopia, and longer axial length tend to have higher FTD and more advanced FT grades.

Galectin-8 involves in arthritic condylar bone loss via podoplanin/AKT/ERK axis-mediated inflammatory lymphangiogenesis.

OBJECTIVE: The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. Galectin-8 (Gal-8) regulates pathological lymphangiogenesis but the effects of which on inflammation-related condylar bone loss in temporomandibular joint (TMJ) have not been well studied. DESIGN: We used TNFα-transgenic (TNFTG) mice and their wildtype (WT) littermates to compare their inflammatory phenotype in TMJs. Next, lymphatic endothelial cells (LECs) were used to examine the effects of which on osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis with or without thiodigalactoside (TDG, a Gal-8 inhibitor) treatment. At last, two murine models (TNFTG arthritic model and forced mouth opening model) were used to explore TDG as a potential drug for the treatment of inflammation-related condylar bone loss. RESULTS: In comparison to WT mice, lymphatic areas of lymphatic vessel endothelial receptor 1 (LYVE1)+/podoplanin (PDPN)+ and Gal-8+/PDPN+, TRAP-positive osteoclast number, and condylar bone loss are increased in TNFTG mice. Inhibition of Gal-8 in LECs by TDG, reduces TNFα-induced osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis. In addition, Gal-8 promotes TNFα-activated AKT/ERK/NF-κB pathways by binding to PDPN. Finally, the administration of TDG attenuates inflammatory lymphangiogenesis, inhibits osteoclast activity, and reduces condylar bone loss in TNFTG arthritic mice and forced mouth opening mice. CONCLUSIONS: Our findings reveal the important role of Gal-8-promoted pathological lymphangiogenesis in inflammation-related condylar bone loss.

High-Flux Neutron Generator Based on Laser-Driven Collisionless Shock Acceleration.

A novel compact high-flux neutron generator with a pitcher-catcher configuration based on laser-driven collisionless shock acceleration (CSA) is proposed and experimentally verified. Different from those that previously relied on target normal sheath acceleration (TNSA), CSA in nature favors not only acceleration of deuterons (instead of hydrogen contaminants) but also increasing of the number of deuterons in the high-energy range, therefore having great advantages for production of high-flux neutron source. The proof-of-principle experiment has observed a typical CSA plateau feature from 2 to 6 MeV in deuteron energy spectrum and measured a forward neutron flux with yield 6.6×10^{7} n/sr from the LiF catcher target, an order of magnitude higher than the compared TNSA case, where the laser intensity is 10^{19} W/cm^{2}. Self-consistent simulations have reproduced the experimental results and predicted that a high-flux forward neutron source with yield up to 5×10^{10} n/sr can be obtained when laser intensity increases to 10^{21} W/cm^{2} under the same laser energy.

Association of edentulism and all-cause mortality in Chinese older adults: do sex differences exist?

OBJECTIVES: Previous studies revealed that tooth loss or edentulism was related to mortality. However, research in developing countries with large numbers of elderly populations is rare, and whether sex differences exist in this relationship is unknown. This study aimed to investigate the association between edentulism and 7-year all-cause mortality among older adults in China and whether sex differences existed. STUDY DESIGN: This was a prospective cohort study. METHODS: Data were from 2011 to 2018 waves of the China Health and Retirement Longitudinal Study. A total of 6538 participants aged ≥60 years were included. Logistic models were adopted to estimate the risks of mortality according to edentulism. RESULTS: The participants with edentulism at baseline were 20% more likely to die over 7 years after controlling for a set of covariates (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.02-1.42). Moreover, edentulism was associated with a 35% higher odds of death among male participants (OR = 1.35, 95% CI: 1.08-1.70), whereas a significant association was not found in female participants. CONCLUSIONS: The findings demonstrated that baseline edentulism predicted all-cause mortality in Chinese older adults, and sex differences existed in this association. This study implied the importance of developing oral health education programs, incorporating dietary recommendations into dental care for edentulous patients, and expanding the coverage of dental services in the health insurance system to prevent edentulism and alleviate its negative outcomes for older adults.

Health inequalities of global protein-energy malnutrition from 1990 to 2019 and forecast prevalence for 2044: data from the Global Burden of Disease Study 2019.

OBJECTIVES: Protein-energy malnutrition poses a serious medical problem worldwide. This study aims to describe the global burden, trends, and health inequalities of protein-energy malnutrition and forecasts for future prevalence. STUDY DESIGN: This was a comprehensive analysis based on data provided by the Global Burden of Disease Study 2019. METHODS: Data were obtained from the Global Health Data Exchange query tool, including prevalence, deaths, disability-adjusted life years (DALYs) and sociodemographic index (SDI). The estimated annual percentage changes were calculated to evaluate temporal trends. We quantified cross-country inequalities in protein-energy malnutrition burden and predicted the prevalence number and rate to 2044. RESULTS: Globally, there were 147,672,757 (130,405,923 to 167,471,359) cases of protein-energy malnutrition in 2019, with 212,242 (185,403 to 246,217) deaths. Eastern Sub-Saharan Africa had the highest age-standardised death and DALY rates in 2019. From 1990 to 2019, the global age-standardised prevalence rate of protein-energy malnutrition showed an upward trend, while the age-standardised death rate showed a downward trend. A significant decline occurred in SDI-related health inequality, from 2126.1 DALYs per 100,000 persons between the poorest and richest countries in 1990 to 357.9 DALYs per 100,000 persons in 2019. There was a trend of decreasing age-standardised death and DALY rates along with increases in the SDI. Frontier analyses showed that there is much room for improving the current situation of protein-energy malnutrition in some countries. In the next 35 years, the prevalence of protein-energy malnutrition will continue to increase. CONCLUSION: Although the disease burden of protein-energy malnutrition has greatly decreased since 1990 and health inequalities between countries are shrinking, the prevalence in Asian and African countries may continue to increase. Focussing on regional differences and strengthening the nutritional intake of people in underdeveloped areas are necessary to reduce future burdens.

American Heart Association's new 'Life's Essential 8' score in association with cardiovascular disease: a national cross-sectional analysis.

OBJECTIVE: The American Heart Association (AHA) has recently updated and enhanced the quantification of cardiovascular health by using the Life's Essential 8 (LE8) score. We intended to examine the correlation between cardiovascular health status, as measured by the new LE8 score, and cardiovascular disease (CVD) in US adults. STUDY DESIGN: National cross-sectional study. METHODS: A total of 24,730 individuals without pregnancy and with complete data from 2007 to 2018 enrolled in the study. The overall LE8 score was divided into low, moderate, and high groups. Multivariate logistic regressions were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the LE8 score and the presence of CVD. RESULTS: Overall, the high LE8 group had a younger age (20-59 years, 82.95%) and more females (60.09%) compared to the low LE8 group. Moderate and high LE8 correlated negatively with the presence of CVD (moderate, OR: 0.46, 95% CI: 0.39-0.54; high, OR: 0.26, 95% CI: 0.21-0.33). One standard deviation increment in the LE8 score correlated significantly with lower odds of CVD (OR: 0.64; 95% CI: 0.60-0.69). Further stratification analysis also detected a significant relationship between the new LE8 score and CVD, and the result was enhanced among the young and women (P-interaction<0.001). CONCLUSIONS: Higher LE8 score correlated with lower odds of CVD, especially among the young and women.

[Pelvic coronal inclination change in adolescent flexible flatfoot surgically treated with arthroereisis].

Objective: To evaluate adolescent pelvic coronal inclination angle change after flatfoot treated with arthroereisis. Method: A case-series study. From June 2018 to September 2020, 25 children with flexible flat foot and pelvic obliquity were included in this retrospective study in Peking University Shenzhen Hospital. There were 17 males and 8 females with a mean age of (11.2±2.2) years (9-15 years). There were 5 cases of unilateral flatfoot and 20 cases of bilateral flatfoot. All of the patients were surgically treated with arthroereisis. Regular follow-up was done in 3 months, 1 and 2 years postoperatively. Weightbearing fluoroscopy of entire lower limb and foot were investigated to measure Meary's angle, calcaneal pitch angle, height difference at ankle and pelvic plane, pelvic inclination and sacrum-iliac distance (F value) on coronal plane. Results: The mean Mearys' angle at 3 month postoperatively was improved when compared with that before the operation (3.1°±1.5° vs 25.9°±4.3°, P<0.001), and it remained at the same level 2 years after the operation (compared with that at 1 year after the operation, P=0.748). The calcaneal pitch angle improved significantly at 3-month follow-up when compared with that before the operation (16.6°±2.4° vs 9.9°±1.5°, P<0.001), and there was no significant change between 1 year and 2 years after operation (P=0.542). The height difference at mortise plane were also reduced at the 3-month follow-up(P<0.001), and it remained at the same level at 1 year and 2 years after the operation (P=0.159). Pelvic height difference decreased dramatically from (12.4±1.7) mm (before operation) to (7.1±1.2) mm(3 month after the operation) (P<0.001), it decreased to (3.6±1.8) mm 1 year after the operation (compared with that at 3 months after the operation, P<0.001), and no further reduction was observed 2 years after the surgery (P=0.483). The pelvic inclination angle and sacrum-iliac distance were also improved at 3-month follow-up when compared with those before the operation (both P<0.001), and they declined further 1 year after the operation(both P<0.05), but the decreasing trend disappeared at the 2-year follow-up (both P>0.05). Conclusion: For adolescent flexible flat foot patients with pelvic obliquity, the coronal inclination and pelvic height discrepancy would partially recovered with correction of flatfoot deformity, but it could not be completely corrected in the mean follow-up period of 2 years after the operation.

[Analysis of typing conversion and perinatal outcomes in twins with selective intrauterine growth restriction of different subtypes].

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.

[The trend of birth weight of full-term newborns and its association with parental reproductive age in Chongqing municipality from 2010 to 2022].

To analyze the trend of abnormal birth weight of full-term newborns and its correlation with parental reproductive age in Chongqing municipality from 2010 to 2022. Based on the Chongqing Birth Certificate System, full-term newborns born from January 2010 to December 2022 were selected. Parental information and birth weight were abstracted from the system. The joinpoint regression model was used to assess the trend of incidence of low birth weight (LBW) and macrosomia in the offspring from 2010 to 2022. The logistic regression model was utilized to analyze the association between parental reproduction age and birth weight of newborns. The average birth weight of 3 155 542 newborns was (3 305.8±410.5) g. The joinpoint regression model showed a decreasing trend for the incidence of LBW from 2010 to 2016 (APC=-4.26%, P<0.05), and an increasing trend from 2020 to 2022 (APC=8.99%, P<0.05). The incidence of macrosomia exhibited a decreasing trend from 2015 to 2022 (APC=-3.37%, P<0.05). The logistic regression model showed that, compared to the group with parents aged 20-34 years, the risk of LBW increased in other age groups. The risk of macrosomia decreased when either parent was aged<20 years, and increased when both parents were aged≥20 years. In conclusion, from 2010 to 2022, the incidence of LBW in full-term offspring in Chongqing municipality decreased first and then increased, and the incidence of macrosomia increased first and then decreased. Both young and advanced parental age were associated with an increased risk of LBW in offspring, and advanced parental age was also associated with an increased risk of macrosomia in offspring. Attention should be paid to the effects of advanced maternal and paternal age on offspring birth weight. Further efforts to control childbearing at a young age were needed.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.