Search

Background/purpose: Pterygoid implant is a promising solution for patients with a partially or fully edentulous atrophic maxilla. However, whether dynamic navigation system will improve the accuracy of pterygoid implant surgery is still unknown. This study aimed to compare the accuracy of dynamic navigation and free-hand approaches in pterygoid implant placement in completely edentulous maxilla models. Materials and methods: Twenty three-dimensional (3D)-printed edentulous maxilla models were assigned to two groups: the dynamic navigation system group and the free-hand group. Two pterygoid implants were planned in the bilateral pterygomaxillary area and then placed in each model. The entry, exit and angle deviations of the pterygoid implants were measured after pre- and post-operative cone-beam CT (CBCT) image fusion. Student's t test and Mann–Whitney U test were used. A P value

Abstract Background Teaching assistants (TAs) play a crucial role in pedagogical practices, and the TA training has emerged as a vital strategy for enhancing teaching quality and fostering effective interactions. The self-efficacy of TAs can substantially impact their performance. Nevertheless, little research has focused on the change in TAs’ self-efficacy following their training. Methods A self-control quasi-experiment was conducted to examine shifts in the self-efficacy of Tas at Peking University before and after their TA training. A questionnaire was used to assess the change, and the reliability and validity of the questionnaire was also calculated. A paired data rank sum test was used to analysis the changes in TA self-efficacy before and after training. Results A total of 372 TAs from School of Basic Medicine (N = 173), School of Pharmacy (N = 112), School of Public Health (N = 69), and other schools (N = 18) submitted complete questionnaires. The questionnaire showed a good performance in internal reliability and validity test (Cronbach’s alpha index = 0.906, and KMO value was 0.903). Participants had a median total self-efficacy score of 88 and 85 before and after the TA training, respectively, which shows a lack in the total TA self-efficacy score following the TA training (P

Abstract Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical. Graphic Abstract

Examining the morphological evolution of ancient Jiande County (JD) over time, our research adopts a diachronic perspective to explore county-level spatial planning and its correlations with local governance during the feudal and republican eras. Utilizing historical records, including chronicles, geo-maps, and remote sensing images, to reconstruct urban ground plans, our findings unveil a historical shift in administrative management within the ancient Yanzhou region (YZ). In the Song Dynasty, feudal authority was distinctly manifested through a spatial hierarchy, diminishing in influence during the Ming-Qing Dynasty. In contemporary times, Meicheng Town (the ancient Jiande County) has departed from traditional urban layouts, relinquishing its central position in the local administrative hierarchy. JD’s historic transition in county-level urban planning and local governance paradigms provides evidence for examing its future development trajectories.

Subtropical Moso bamboo (Phyllostachys edulis) forests have become hot spots for nitrogen (N) deposition in China. However, the effect of long-term N deposition on the structure of soil microbial communities in different horizons of these forests remains unclear. To investigate the influence of extended N deposition on soil bacteria and fungi, a simulated N deposition field study was conducted in Fujian Province with four N deposition levels (0, 20, 40 and 80 kg N hm−2 a−1). The absolute abundances, diversity, community structure, and potential functions of soil bacteria and fungi were investigated after 10 years of simulated N deposition. The results indicated that there was no significant effect of N deposition on the abundance or diversity of soil microbes in either the organic or mineral horizons of Moso bamboo forests. However, under rates of 40 and 80 kg N hm−2 a−1, long-term N deposition altered the structure of the soil bacterial community in the organic horizon. Specifically, there was a 27.75∼36.40 % increase in the relative abundance of Actinobacteria, while that of Acidobacteria decreased by 24.40∼27.52 %. Redundancy analysis (RDA) demonstrated that soil total carbon (TC) was the key variable influencing the bacterial community structure in the organic horizon. Analysis of potential microbial functions showed that in the organic horizon, the rates of chemoheterotrophy significantly decreased under 80 kg N hm−2 a−1. However, N deposition did not noticeably impact the fungal community structure in either soil horizon. Our study suggested that under 10 years of N deposition, only the bacterial community composition and function in the organic horizon was affected, indicating that soil bacteria are more sensitive to N deposition than fungi in subtropical Moso bamboo forests. Therefore, further research is necessary to fully understand the impact of N deposition on fungal community composition in the soil organic horizon and on the microbial community in the mineral horizon of subtropical bamboo forests. This study provides valuable insights for informing future environmental management and conservation strategies.

Abstract Background Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. Methods By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). Findings Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18–0.19) to 0.23 (95% CI 0.23–0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. Interpretation Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of ‘Long COVID-19.’

Abstract Purpose We assessed the efficiency of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomimetic calcium phosphate on β-tricalcium phosphate (β-TCP) (rhBMP-2/BioCaP/β-TCP) on bone formation in a model of socket preservation using cone beam computed tomography (CBCT) scanning and histological examination. Methods Forty patients undergoing minimally invasive single-root tooth extraction for dental implantation were randomized to three groups according to the material used for socket preservation: filling with rhBMP-2/BioCaP/β-TCP, β-TCP, or natural healing (kept unfilled) (controls). The alveolar sockets (including the control group) were covered by two-layer collagen membranes and sutured. Two CBCT scans were taken, one immediately after socket preservation procedure (baseline) and another 6 weeks later. Gray values (GVs) obtained from CBCT were recorded. During insertion of the dental implant, biopsies were taken and analyzed histologically for new bone formation, residual material, and unmineralized bone tissue at the core of the biopsy. Results The mean (± standard deviation) changes of GVs of the CBCT scans at the central area of filled materials were as follows: 373.19 ± 157.16 in the rhBMP-2/BioCaP/β-TCP group, 112.26 ± 197.25 in the β-TCP group, and -257 ± 273.51 in the control group. The decrease of GVs in the rhBMP-2/BioCaP/β-TCP group as compared with the β-TCP group was statistically significant (P

Coordinating the relationship between new-type urbanization (NTU) and carbon emission (CE) reduction has emerged as a primary strategic objective in China. However, previous studies on this subject have predominantly focused on the unidirectional impact of NTU on CE, neglecting their spatio-temporal characteristics and the potential for a decoupling relationship. Focusing on the county-level areas in Zhejiang Province, this study establishes an evaluation system for measuring NTU and investigates the spatio-temporal characteristics and evolving decoupling relationship of NTU and CE from 2007 to 2021, along with the influencing factors. The results are shown as follows: (1) CE levels in Zhejiang's counties are predominantly higher in the northeast and lower in the southwest, with minimal temporal fluctuations. Concurrently, the collective NTU in these counties has witnessed a rapid increase, with a growing disparity in NTU levels and a concentration of higher NTU primarily in the northern regions. (2) From 2007 to 2021, the decoupling relationship between NTU and CE in Zhejiang's counties evolved from suboptimal to significantly improved, ultimately achieving continuous optimization, with the proportion of counties in the “strong decoupling II” category increasing to 60.7% in the final phase. (3) The most significant influencing factors for decoupling evolved from economic NTU predominance in 2007 to societal NTU in 2012, and further progressed to population NTU in 2022. (4) Informed by the types of decoupling and evolutionary factors, we propose strategies and implications aimed at fostering the high-quality, synergistic development of NTU and CE. These findings provide theoretical and empirical underpinnings for the high-quality attainment of NTU and the dual carbon objectives in China.

Abstract Objectives The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. Materials and methods Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. Results A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. Conclusions Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36–141.6 months (3–11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient’s perspective.

Abstract Purpose The purpose of this study was to perform a systematic review with meta-analysis on the long-term survival rates of zygomatic implants (ZI). ZI success, prostheses survival and success, sinus pathology and patient reported outcomes were also investigated. Methods Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. Embase and OvidMedline databases were searched alongside the grey literature. The systematic review was recorded in PROSPERO (CRD42022358024). Studies reporting titanium/titanium alloy ZI survival data, ZI-supported prosthesis data, ZIs directly compared to any other implant therapy including grafted sites, a minimum follow-up time of 3 years and a minimum number of 10 patients were included. All study designs were considered if they met the inclusion criteria. Studies not involving ZIs, ZIs not made from titanium/titanium alloy, a follow-up time of

Abstract Purpose The study aims to use cone beam computed tomography (CBCT) to (1) define the virtual valid length of pterygoid implants in maxillary atrophic patients from the prosthetic prioritized driven position and (2) measure the implant length engaged in the pterygoid process according to the HU difference of the pterygoid maxillary junction. Materials and methods Virtual pterygoid implants were planned with CBCT of maxillary atrophic patients in the software. The entry and angulation of the implant were planned according to the prosthetic prioritized driven position in the 3D reconstruction image. The planned implant length and the valid length defined as the implant between the pterygoid maxillary junction and pterygoid fossa were recorded. The relationship between the implant and sinus cavity was also evaluated. Results A total of 120 CBCT samples were enrolled and virtually planned. The mean age of the patients was 56.2 ± 13.2 years. One hundred and sixteen samples could successfully place virtual implants according to the criterion. The mean implant length and mean implant length beyond the pterygoid maxillary junction were 16.3 ± 4.2 mm (range, 11.5–18 mm) and 7.1 ± 3.3 mm (range, 1.5–11.4 mm), respectively. Ninety percent of virtually planned implants had a close relationship with the sinus cavity, and implants exhibited longer lengths when they had no relation with the sinus. Conclusion From a prosthetic prioritized driven position with fixed entry and angulation, pterygoid implants achieve adequate bone anchorage length beyond the pterygoid maxillary junction. Due to the individual anatomy and the volume of the maxillary sinus, the implants presented a different positional relationship with the maxillary sinus. Graphical Abstract

Abstract Objectives To investigate the potential influence of different grafting materials on maxillary sinus membrane dimensions and ostium patency following lateral sinus floor elevation (SFE) as assessed using cone-beam computed tomography (CBCT). Materials and methods A total of 40 sinuses in 40 patients were included. Twenty sinuses were referred for SFE with deproteinized bovine bone mineral (DBBM), and the remaining 20 sinuses were grafted with calcium phosphate (CP). CBCT was performed prior to and 3 to 4 days after surgery. The dimensions of the Schneiderian membrane volume and ostium patency were evaluated, and potential relationships between volumetric changes and any associated factors were analyzed. Results The median increase in membrane-whole cavity volume ratios was 43.97% in the DBBM group and 67.58% in the CP group, demonstrating no statistically significant difference (p = 0.17). The rates of increased obstruction after SFE were 11.1% for the DBBM group versus 44.4% for the CP group (p = 0.03). The graft volume was found to be positively correlated with the postoperative membrane-whole cavity volume ratio (r = 0.79; p < 0.01) and the membrane-whole cavity volume ratio increase (r = 0.71; p < 0.01). Conclusions The two grafting materials seem to have a similar effect on transient volumetric changes in the sinus mucosa. However, the choice of grafting material should still be made with caution since sinuses grafted using DBBM exhibited less swelling and less ostium obstruction.

EDA variants are associated with X-linked hypohidrotic dysplasia. Here, the authors report the crystal structure of the human EDA-EDAR complex, reveal the important role of this complex in ectodermal development and uncover the structural mechanism of disease-related mutations in EDA.

Significant carbon emissions, a key contributor to global climate warming, pose risks to ecosystems and human living conditions. It is crucial to monitor the spatial and temporal patterns of carbon emissions at the county level to reach the goals of carbon peak and neutrality. This study examines carbon emissions and economic and social problems data from 89 counties in Zhejiang Province. It employs analytical techniques such as LISA time path, spatio-temporal transition, and standard deviational ellipse to investigate the trends of carbon emissions from 2002 to 2022. Furthermore, it utilizes the GTWR model to evaluate the factors that influence these emissions on a county scale. The findings reveal the following: (1) The LISA time path analysis indicates a pronounced local spatial structure in the distribution of carbon emissions in Zhejiang Province from 2002 to 2022, characterized by increasing stability, notable path dependency, and some degree of spatial integration, albeit with a diminishing trend in overall integration. (2) The LISA spatio-temporal transition analysis indicates significant path dependency or lock-in effects in the county-level spatial clustering of carbon emissions. (3) Over the period 2002–2022, the centroid of carbon emissions in Zhejiang’s counties mainly oscillated between 120°55′15″ E and 120°57′01″ E and between 29°55′52″ N and 29°59′11″ N, with a general northeastward shift forming a “V” pattern. This shift resulted in a stable “northeast–southwest” spatial distribution. (4) Factors such as population size, urbanization rate, and economic development level predominantly accelerate carbon emissions, whereas industrial structure tends to curb them. It is crucial to customize carbon mitigation plans to suit the circumstances of each county. This study provides insight into the spatial and temporal patterns of carbon emissions at the county level in Zhejiang Province. It offers crucial guidance for developing targeted and practical strategies to reduce carbon emissions.

Evidence for the health effects of ambient PM1 (particulate matter with an aerodynamic diameter ≤ 1 µm) pollution is limited, and it remains unclear whether a smaller particulate matter has a greater impact on human health. We conducted a time-series study in 184 major cities by extracting daily hospital data on admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and stroke between 2014 and 2017 from a medical insurance claims database of 0.28 billion beneficiaries. City-specific associations were estimated with over-dispersed generalized additive models. A random-effects meta-analysis was used to estimate regional and national average associations. We conducted stratified and meta-regression analyses to explore potential effect modifiers of the association. We recorded 8.83 million cardiovascular admissions during the study period. At the national-average level, a 10-μg/m3 increase in same-day PM1, PM2.5(particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10(particulate matter with an aerodynamic diameter ≤ 10 µm) concentrations corresponded to a 1.14% (95% confidence interval 0.88–1.41%), 0.55% (0.40–0.70%), and 0.45% (0.36–0.55%) increase in cardiovascular admissions, respectively. PM1 exposure was also positively associated with all cardiovascular disease subtypes, including ischemic heart disease (1.28% change; 0.99–1.56%), heart failure (1.30% change; 0.70–1.91%), heart rhythm disturbances (1.11% change; 0.65–1.58%), and ischemic stroke (1.29% change; 0.88–1.71%). The associations between PM1 and cardiovascular admissions were stronger in cities with lower PM1 levels, higher air temperatures and relative humidity, as well as in subgroups with elder age (all P

Abstract Background Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. Method A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. Results We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P

BackgroundMetformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China.MethodsAll patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.ResultsAmong 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend 2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P

Background. Aspiration pneumonia (AP) is difficult to diagnose and has poor outcomes. This case-control study aimed to explore the risk factors and delineate the antibiotic usage for AP. Methods. Inpatients diagnosed with community-acquired pneumonia (CAP) from 2013 to 2017, enrolled in the urban employee basic medical insurance program in Beijing, were included and classified into the AP (N = 2,885) and non-AP (N = 53,825) groups. Risk factors were identified by logistic regression. Results. Older age (compared to 18–64 years, OR for 65–79 years: 4.3, 95% CI: 3.8–4.9; OR for >80 years: 6.3, 95% CI: 5.6–7.2), male (OR: 1.4, 95% CI: 1.3–1.5), cerebrovascular disease (OR: 3.1, 95% CI: 2.8–3.5), dementia (OR: 2.0, 95% CI: 1.8–2.1), vomiting (OR: 1.4, 95% CI: 1.2–1.7), Parkinson’s disease (OR: 2.1, 95% CI: 1.8–2.4), and epilepsy (OR: 3.2, 95% CI: 2.8–3.7) were associated with an increased risk of AP. 92.8% of the AP patients received antibiotic therapy. Among them, patients treated with broad-spectrum antibiotics, antibiotics for injection, and combined antibiotics accounted for 93.3%, 97.9%, and 81.7%, respectively. Conclusions. Older age, male, and several comorbidities were independent risk factors for AP, and combined antibiotics treatments are common, which merits attention in accurate detection of AP in a high-risk population.

Abstract Two-dimensional (2D) Titanium nanosheets (Ti NSs) have shown many excellent properties, such as nontoxicity, satisfactory photothermal conversion efficacy, etc. However, the biomedical applications of Ti NSs have not been intensively investigated. Herein, we synthesized a multifunctional Ti NS drug delivery system modified with polydopamine/polyethylene glycol (Ti@PDA-PEG) and applied simultaneously for photothermal therapy and chemotherapy. Doxorubicin (DOX) was utilized as a model drug. Ti@PDA-PEG NS shows an ultrahigh antitumor drug DOX loading (Ti@PDA-PEG-DOX). The prepared Ti@PDA-PEG-DOX NS as robust drug delivery system demonstrates great stability and excellent multi-response drug-release capabilities, including pH-responsive and near-infrared -responsive behavior and obviously high photothermal efficiency. Both in vitro and in vivo experimental results have shown high biosafety and outstanding antitumor effects. Therefore, this work exhibits the enormous potential of a multifunctional platform in the treatment of tumors and may stimulate interest in the exploration of other new 2D nanomaterials for biomedical applications. Graphical Abstract

Abstract Cardiac damage in non-severe patients with coronavirus disease 2019 (COVID-19) is poorly explored. This study aimed to explore the manifestations of cardiac damage at presentation in non-severe patients with COVID-19. In this study, 113 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: group 1 (≤ 1 week, n = 27), group 2 (> 1 to 2 weeks, n = 28), group 3 (> 2 to 3 weeks, n = 27), group 4 (> 3 weeks, n = 31). Clinical, cardiovascular, and radiological data on hospital admission were compared across the four groups. The level of high sensitivity troponin I (hs-cTnI) in group 2 [10.25 (IQR 6.75–15.63) ng/L] was significantly higher than those in group 1 [1.90 (IQR 1.90–8.80) ng/L] and group 4 [1.90 (IQR 1.90–5.80) ng/L] (all P bonferroni

Purpose: The present systematic review aimed to investigate the accuracy of zygomatic implant (ZI) placement using dynamic computer-aided surgery (d-CAIS), static computer-aided surgery (s-CAIS), and a free-hand approach in patients with severe atrophic edentulous maxilla and/or deficient maxilla. Methods: Electronic and manual literature searches until May 2023 were performed in the PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases. Clinical trials and cadaver studies were selected. The primary outcome was planned/placed deviation. Secondary outcomes were to evaluate the survival of ZI and surgical complications. Random-effects meta-analyses were conducted and meta-regression was utilized to compare fiducial registration amounts for d-CAIS and the different designs of s-CAIS. Results: A total of 14 studies with 511 ZIs were included (Nobel Biocare: 274, Southern Implant: 42, SIN Implant: 16, non-mentioned: 179). The pooled mean ZI deviations from the d-CAIS group were 1.81 mm (95% CI: 1.34–2.29) at the entry point and 2.95 mm (95% CI: 1.66–4.24) at the apex point, and angular deviations were 3.49 degrees (95% CI: 2.04–4.93). The pooled mean ZI deviations from the s-CAIS group were 1.19 mm (95% CI: 0.83–1.54) at the entry point and 1.80 mm (95% CI: 1.10–2.50) at the apex point, and angular deviations were 2.15 degrees (95% CI: 1.43–2.88). The pooled mean ZI deviations from the free-hand group were 2.04 mm (95% CI: 1.69–2.39) at the entry point and 3.23 mm (95% CI: 2.34–4.12) at the apex point, and angular deviations were 4.92 degrees (95% CI: 3.86–5.98). There was strong evidence of differences in the average entry, apex, and angular deviation between the navigation, surgical guide, and free-hand groups (p < 0.01). A significant inverse correlation was observed between the number of fiducial screws and the planned/placed deviation regarding entry, apex, and angular measurements. Conclusion: Using d-CAIS and modified s-CAIS for ZI surgery has shown clinically acceptable outcomes regarding average entry, apex, and angular deviations. The maximal deviation values were predominantly observed in the conventional s-CAIS. Surgeons should be mindful of potential deviations and complications regardless of the decision making in different guide approaches.

Background: Previous evidence yielded contradictory findings on the relationship between metformin and anemia. This study aims to assess whether metformin use is associated with iron-deficiency anemia (IDA) risk in patients with type 2 diabetes (T2D) in Beijing, China. Methods: Overall, 60,327 newly diagnosed T2D patients were included based on a historical cohort study design. The information pertaining to these patients was gathered from the Beijing Medical Claim Data for Employees Database. These patients were then categorized into the metformin and non-metformin groups and matched on a 1:1 propensity score based on their initial antidiabetic prescription. The Cox proportional hazards models were utilized to calculate the incidences and the hazard ratios (HRs). Results: The study enrolled 27,960 patients with type 2 diabetes, with 13,980 patients in each of the initial glucose-lowering prescription groups: metformin and non-metformin. During a median follow-up period of 4.84 years, 4832 patients developed IDA. The incidence of IDA was significantly lower in the metformin group (26.08/1000 person-years) than in the non-metformin group (43.20/1000 person-years). Among the three groups divided by the proportion of days covered by metformin, we found a negative correlation between the proportion of days covered by metformin and the risk of IDA. The risk of IDA in patients with a proportion of days covered by metformin of

BackgroundLoop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia.MethodsEighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system.ResultsCCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1–70.5; p

ObjectiveHyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management.MethodsWe tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes.ResultsTraditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72–0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258).ConclusionsWe verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.

Abstract Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype–phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.

ObjectiveTo investigate emergency medical service (EMS) utilization and its associated factors in patients with acute ischemic stroke (AIS), and further explore the urban-rural differences.MethodsMedical records for AIS in all emergency departments in Beijing were obtained from the Beijing Emergency Care Database from January 2018 to December 2021. EMS utilization was described and factors associated with EMS use were examined by multivariable logistic regression models with the generalized estimating equations. Results were compared between urban and rural districts.ResultsA total of 24,296 AIS patients were included in the analysis, and 11,190 (46.1%) were transported to hospitals by EMS. The percentage of EMS usage in urban areas was significantly higher than that in rural areas (53.6 vs. 34.4%, P < 0.001). From 2018 to 2021, EMS utilization was on the increase (P-value for trend

Soil microbes are the key to revealing the mechanisms driving variation in soil biogeochemical processes. In recent decades, forests in Southeast China have been widely transformed into tea plantations due to the drivers of economic benefits. However, the changes in the soil microbial community and their potential function during the transition from a typical forest ecosystem to tea plantations remain poorly understood. This study investigated the soil microbial community in tea plantation soils with different planting ages, i.e., 6, 12, 23 and 35 years, and in an adjacent woodland control. We discovered that tea planting significantly increased soil bacterial richness (ACE and Chao1) and decreased fungal richness, the diversity of bacteria (Simpson and Shannon) show a trend of initially decreasing and then increasing while there was no significant effect on fungal diversity. After tea planting, the relative abundances of Actinobacteria and Proteobacteria increased by 180.9%–386.6% and 62.3%–97.5%, respectively; the relative abundances of Acidobacteria decreased by 11.4%–66.8%. However, the fungal phyla were not significantly different among different aged tea plantations and woodlands. FAPROTAX and FUNGuild revealed that the transition of natural woodland to tea plantations significantly increased the relative abundances of aerobic_chemoheterotrophy (14.66%–22.69%), chemoheterotrophy (34.36%–37.04%), ureolysis (0.68%–1.35%) and pathogenic fungi (26.17%–37.02%). db-RDA proved that the bacterial community structure was more strongly related to soil pH and available nitrogen (AN), while the main determinants of the fungal community composition were soil pH and soil organic matter (SOM). These findings indicate that tea planting has a strong effect on the soil microbial community and potential function. The change in soil pH during tea planting was the most important factor affecting the soil microbial community, while soil bacteria were more sensitive to tea planting than fungi.

Abstract Information on the clinical staging of coronavirus disease 2019 (COVID-19) is still limited. This study aimed to propose a clinical staging proposal of the disease course in non-severe patients with COVID-19. In this retrospective study, 108 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: ≤ 1 week, > 1 to 2 weeks, > 2 to 3 weeks, > 3 to 5 weeks, respectively. The dynamic changes of clinical signs were profiled across the four groups. A clinical staging proposal of the disease course over time was proposed from the perspective of the interaction between the virus and host. The prodromal phase, characterized by pneumonia, significant lymphopenia, and slightly elevated inflammatory markers, occurred in the first week after symptoms onset. In the second week, all the hematological and inflammatory markers were at the peak or bottom. Meanwhile, progressive pneumonia as well as the secondary damage of other organs (e.g. cardiac damage, coagulopathy, etc.) was significant during this period, making the disease progress into the apparent manifestation phase. In the third week, the improvement of the majority of clinical signs accompanied by a relatively high degree of inflammatory response defined the remission phase. After 3 weeks, patients were in the convalescent phase, in which all the indicators were maintained at a relatively normal level. We concluded that the disease course over time in non-severe patients with COVID-19 could be divided into four phases: the prodromal phase (in the first week), the apparent manifestation phase (in the second week), the remission phase (in the third week), and the convalescent phase (after 3 weeks), respectively. In clinical practice, tailored therapies should be considered seriously in different stages of the disease course.

Background: The congenital oligodontia in maxilla could result in a significant skeletal jaw malformation such as atrophic maxilla and severe skeletal class III malocclusion. Since there is no referable dentition in anterior maxilla, the orthognathic surgery and oral rehabilitation for those patients becomes more challenging and less predictable. Materials and methods: We hereby present a new sequencing of interdisciplinary treatments, including calvarial bone grafting, installation of implant-supported provisional prosthesis, bimaxillary orthognathic surgery, and the final installation of dental implants and the fixed prosthesis. Results: The facial esthetics and function of the permanent prosthesis were satisfactory, with a remarkable improvement in the maxillomandibular relation, adequate horizontal and vertical repositioning of the maxilla, and appropriate incisor exposure. Conclusion: Although more surgeries and longer treatment period may be required due to the interdisciplinary treatment plan, better aesthetic and functional outcomes may be acquired by this reported procedure in the long-term for young patients.

While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy.

BackgroundIntravenous thrombolysis and endovascular thrombectomy have been approved for acute ischemic stroke (AIS). However, only a minority of patients received these treatments in China. We aimed to evaluate the efficacy and safety of tirofiban in patients with AIS who were not undergoing early recanalization treatments.MethodsPatients with mild-to-moderate stroke [National Institutes of Health Stroke Scale (NIHSS) score, 4–15] were enrolled in this study. Patients due to cardiogenic embolism were excluded. Eligible patients within 12 h from symptom onset were randomly assigned (1:1) to receive tirofiban (a loading dose of 0.4 μg/kg/min over 30 min and a maintenance dose of 0.1 μg/kg/min up to 48 h) followed by regular treatment or to receive regular treatment (aspirin at a dose of 100 mg per day for 90 days) (control). The primary outcome was the proportion of favorable functional outcomes at 90 days [defined as the modified Rankin Scale (mRS) score of 0–2]. The secondary outcomes included a shift in the distribution of the mRS scores at 90 days and the NIHSS score at 24 h and 7 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 7 days after tirofiban treatment.ResultsA total of 380 eligible patients were randomly assigned to the tirofiban group (n = 190) or the control group (n = 190). The proportion of favorable functional outcomes was higher in the tirofiban group (79.1%) than that in the control group (67.8%) at 90 days [odds ratio (OR), 1.80; 95% CI, 1.12–2.90; p = 0.0155]. An improvement was also observed in the overall distribution of the 90-day mRS scores (adjusted common OR, 2.31; 95% CI, 1.58–3.39; p < 0.0001). Additionally, the median NIHSS score was lower in the tirofiban group than in the control group at 7 days (3 vs. 5, p < 0.0001). Next, we observed that the occurrence of sICH did not differ between the two groups.ConclusionOur trial supports that tirofiban was safe and effective and might be a remedial treatment for patients with AIS who did not receive recanalization treatments.Clinical Trial Registrationhttp://www.chictr.org.cn/, identifier: ChiCTR2000031297.

Light-field raw data captured by a state-of-the-art light-field camera is limited in its spatial and angular resolutions due to the camera's optical hardware. In this paper, we propose an all-software algorithm to synthesize light-field raw data from a single RGB-D input image, which is driven largely by the need in the research area of light-field data compression. Our synthesis algorithm consists of three key steps: (1) each pixel of the input image is regarded as a spot lighting source that emits directional light rays with an equal strength; (2) the optical path of each directional light ray through the camera's main lens as well as the corresponding micro lens is considered as accurately as possible; and (3) the occlusion of light rays among objects at different distances within the input image is handled with the depth information. The spatial and angular resolutions of our synthesized light-field data can be scaled up when the input RGB-D image has a higher and higher spatial resolution. Meanwhile, for a given input image with a fixed size, we pay a special attention to what would be the extreme we can push the parameters involved in our synthesis algorithm, such as the number of rays emitted from each pixel, the number of micro lenses, and the number of sensors associated with each micro lens. The usefulness of our synthesized data is validated by refocusing, all-in-focus, and sub-aperture reconstructions. In particular, all-in-focus images are evaluated objectively by computing the structural similarity (SSIM) index, which allows us to reach the goal of pushing to the extreme through selecting various parameters mentioned above.

The aggregation and interaction of metabolic risk factors leads to highly heterogeneous pathogeneses, manifestations, and outcomes, hindering risk stratification and targeted management. To deconstruct the heterogeneity, we used baseline data from phase II of the Fangshan Family-Based Ischemic Stroke Study (FISSIC), and a total of 4632 participants were included. A total of 732 individuals who did not have any component of metabolic syndrome (MetS) were set as a reference group, while 3900 individuals with metabolic abnormalities were clustered into subtypes using multi-trait limited mixed regression (MFMR). Four metabolic subtypes were identified with the dominant characteristics of abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic regression showed that the hyperglycemia-dominant subtype had the highest coronary heart disease (CHD) risk (OR: 6.440, 95% CI: 3.177–13.977) and that the dyslipidemia-dominant subtype had the highest stroke risk (OR: 2.450, 95% CI: 1.250–5.265). Exome-wide association studies (EWASs) identified eight SNPs related to the dyslipidemia-dominant subtype with genome-wide significance, which were located in the genes APOA5, BUD13, ZNF259, and WNT4. Functional analysis revealed an enrichment of top genes in metabolism-related biological pathways and expression in the heart, brain, arteries, and kidneys. Our findings provide directions for future attempts at risk stratification and evidence-based management in populations with metabolic abnormalities from a systematic perspective.

The single nucleotide polymorphism (SNP) rs4148727 in ABCB1 (encoding p-glycoprotein) is associated with lipid levels; however, its association with type 2 diabetes (T2DM) and its the genetic correlation with lipid profiles and T2DM are unclear. We included 2300 participants from 593 families. A generalized estimating equations (GEE) model and Cox regression models were used to estimate the SNP’s effects on T2DM and lipid profiles. The participation of the SNP in T2DM pathogenesis through lipid-associated pathways was tested using mediation analysis. The G allele of the SNP was related to a 32% (6–64%, p = 0.015) increase in T2DM risk. It was also associated with a 10% (1–20%, p = 0.029), 17% (3–32%, p = 0.015), and 4% (1–7%, p = 0.015) increment in total cholesterol (TC), triglyceride (TG), and apolipoprotein A (Apo-A) concentrations, respectively. According to the mediation analysis, only TG (6.9%) and Apo-B (4.0%) had slight but significant mediation effects on the total impact of the SNP on T2DM. The pleiotropic effects of the ABCB1 variant on T2DM and lipids likely act via different pathways. The biological mechanisms should be verified in a future study.

Glucosamine is widely used around the world and as a popular dietary supplement and treatment in patients with osteoarthritis in China; however, the real-world cardiovascular risk of glucosamine in long-term use is still unclear. A retrospective, population-based cohort study was performed, based on the Beijing Medical Claim Data for Employees from 1 January 2010 to 31 December 2017. Patients newly diagnosed with osteoarthritis were selected and divided into glucosamine users and non- glucosamine users. The glucosamine users group was further divided into adherent, partially adherent, and non-adherent groups according to the medication adherence. New-onset cardiovascular diseases (CVD) events, coronary heart diseases (CHD), and stroke, were identified during the observational period. COX proportional regression models were used to estimate the risks. Of the 685,778 patients newly diagnosed with osteoarthritis including 240,419 glucosamine users and 445,359 non-users, the mean age was 56.49 (SD: 14.45) years and 59.35% were females. During a median follow-up of 6.13 years, 64,600 new-onset CVD, 26,530 CHD, and 17,832 stroke events occurred. Glucosamine usage was significantly associated with CVD (HR: 1.10; 95% CI: 1.08–1.11) and CHD (HR: 1.12; 95% CI: 1.09–1.15), but not with stroke (HR: 1.03; 95% CI: 0.99–1.06). The highest CVD risk was shown in the adherent group (HR: 1.68; 95% CI: 1.59–1.78), followed by the partially adherent group (HR: 1.26, 95% CI: 1.22–1.30), and the non-adherent group (HR: 1.03; 95% CI: 1.02–1.05), with a significant dose–response relationship (p-trend < 0.001). In this longitudinal study, adherent usage of glucosamine was significantly associated with a higher risk for cardiovascular diseases in patients with osteoarthritis.

Objective: Few studies have been concerned with the combined influences of the presence of multiple risk factors on follow-up outcomes in AMI patients. Our study aimed to identify risk factor patterns that may be associated with 1-year survival in male patients with ST-segment elevation myocardial infarction (STEMI).Methods: Data were from the China STEMI Care Project Phase 2 (CSCAP-2) collected between 2015 and 2018. A total of 15,675 male STEMI patients were enrolled in this study. Risk factor patterns were characterized using latent class analysis (LCA) according to seven risk factors. Associations between risk factor patterns and follow-up outcomes, including the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death, were investigated by Cox proportional hazard regression analysis.Results: We obtained four risk factor patterns as “young and middle-aged with low levels of multimorbidity,” “middle-aged with overweight,” “middle-aged and elderly with normal weight,” and “elderly with high multimorbidity.” Four patterns had significant differences in event-free survival (P < 0.001). As compared with the patients of “young and middle-aged with low levels of multimorbidity” pattern, the risk of incidence of MACCE and all-cause death were increased in patients of “middle-aged with overweight” pattern (All-cause death: HR = 1.70, 95% CI:1.29~2.23; MACCE: HR = 1.49, 95% CI:1.29~1.72), “middle-aged and elderly with normal weight” pattern (All-cause death: HR = 3.04, 95% CI: 2.33~3.98; MACCE: HR = 1.82, 95% CI: 1.56~2.12), and “elderly with high multimorbidity” pattern (All-cause death: HR = 5.78, 95% CI: 4.49~7.42; MACCE: HR = 2.67, 95% CI: 2.31~3.10).Conclusions: By adopting a Latent Class Analysis Approach, STEMI patients can be characterized into four risk factor patterns with significantly different prognosis. The data is useful for the improvement of community health management in each specific subgroup of patients, which indicates a particular risk factor pattern.

This paper examines the role of international trade for economic prosperity in Pacific island countries (PICs), discusses their comparative advantage, and explores the potential for trade, and tourism in particular, to serve as a locomotive for inclusive economic growth. We find the trade performance in PICs has been generally weak over the past decade, with the exception of resource-rich countries. Small country size and remoteness from global economic centers may have contributed to this relatively poor performance. Using the gravity models to analyze the determinants of merchandise trade and tourism in PICs, we find tourism in these countries faces more favorable conditions for growth than goods exports. Further, we place our analysis in the context of the eastward shift of global economic gravity, focusing on emerging Asia as a source of demand for resource-based goods and services. We argue that the emergence of Asia as a dynamic global economic region presents PICs with an unprecedented opportunity to develop trade, particularly tourism, although traditional markets will remain important for a long time to come. Moreover, if stronger synergies can be established between tourism, agriculture, and fisheries, Pacific island countries stand a better chance to improve broad-based growth.

Abstract Background Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. Methods Western blotting and qPCR were performed to investigate the influences of miRNA-21 on osteogenic differentiation of BMSCs. The effects of miRNA-21 on PTEN/PI3K/Akt/HIF-1α pathway were also assessed using western blotting. To further evaluate the roles of miRNA-21 in osteogenesis in vivo, we conducted animal experiments in rat and canine. New bone formation was assessed using micro-CT and histological methods. Results In the present study, we found that miRNA-21 promotes the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro. Using gain- and loss-of-function studies, we found that miRNA-21 promoted the osteogenic ability of BMSCs by increasing P-Akt and HIF-1α activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/β-tricalcium phosphate (β-TCP) composite into critical size defects. Radiography, micro-CT, and histology revealed significantly greater volume of new bone formation in the miRNA-21 group than in the control group. Conclusion In conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1α pathway.

Background: Rapid and effective medical care for stroke is paramount to achieve maximal functional recovery. Because of the wide spreading of the coronavirus disease in 2019 (COVID-19), acute stroke care is negatively impacted. How much acute care for stroke has been affected during the pandemic remains to be assessed.Methods: The first-level response to major public health was launched from January 24th to April 29th, 2020 in Beijing to contain the spread of COVID-19. Based on a database connecting all 77 stroke centers, the quantity and quality in emergency care for stroke during the 97 lockdown days were compared with the equivalent period in 2019. During the pandemic, 15 of the 77 stroke centers were designated to receive patients sick with COVID-19. Subgroup analyses were carried out by different types of hospitals (designated and undesignated).Results: There were 1,281 and 2,354 stroke emergency hospital admissions in the lockdown period and the parallel period in 2019, respectively. A reduction of 45.6% in admission was shown in the lockdown period, with more reductions for hemorrhagic stroke (69.0%) compared with ischemic stroke (42.9%). More reductions happened in COVID-19 designated hospitals (52.6%) compared with undesignated hospitals (41.8%). The mean NIHSS score at hospital arrival was significantly higher in the lockdown period (9.4 ± 7.7 in 2020 vs. 8.4 ± 7.8 in 2019, P < 0.001). For the metrics measuring the quality of acute stroke care, the onset to door (OTD), onset to needle (ONT), and onset to recanalization (OTR) times didn't change significantly, while significant delays are shown for the door to CT scan (DTC, 1 min delay), door to needle (DTN, 4 min delays), and door to puncture (DTP, 29 min delays) times, which mainly happened in COVID-19 undesignated hospitals.Conclusions: Profound reductions in stroke hospital admissions and significant delays in emergency care for acute ischemic stroke occurred during the pandemic of COVID-19. Engagement and effective communication with all stakeholders including patients, health care providers, governmental policymakers, and other implementation partners are required for future success in similar crises.

Conventional antitumor chemotherapeutics generally have shortcomings in terms of dissolubility, selectivity and drug action time, and it has been difficult to achieve high antitumor efficacy with single-drug therapy. At present, combination therapy with two or more drugs is widely used in the treatment of cancer, but a shortcoming is that the drugs do not reach the target at the same time, resulting in a reduction in efficacy. Therefore, it is necessary to design a carrier that can release two drugs at the same site. We designed an injectable pH-responsive OE peptide hydrogel as a carrier material for the antitumor drugs gemcitabine (GEM) and paclitaxel (PTX) that can release drugs at the tumor site simultaneously to achieve the antitumor effect. After determining the optimal gelation concentration of the OE polypeptide, we conducted an in vitro release study to prove its pH sensitivity. The release of PTX from the OE hydrogel in the medium at pH 5.8 and pH 7.4 was 96.90% and 38.98% in 7 days. The release of GEM from the OE hydrogel in media with pH of 5.8 and 7.4 was 99.99% and 99.63% in 3 days. Transmission electron microscopy (TEM) and circular dichroism (CD) experiments were used to observe the microstructure of the peptides. The circular dichroism of OE showed a single negative peak shape when under neutral conditions, indicating a β-folded structure, while under acidic conditions, it presented characteristics of a random coil. Rheological experiments were used to investigate the mechanical strength of this peptide hydrogel. Furthermore, the treatment effect of the drug-loaded peptide hydrogel was demonstrated through in vitro and in vivo experiments. The results show that the peptide hydrogels have different structures at different pH values and are highly sensitive to pH. They can reach the tumor site by injection and are induced by the tumor microenvironment to release antitumor drugs slowly and continuously. This biologically functional material has a promising future in drug delivery for combination drugs.

Accumulating evidence suggests a relationship between type 2 diabetes mellitus and sleep problems. A comprehensive study is needed to decipher whether shared polygenic risk variants exist between diabetic traits and sleep traits. Methods: We integrated summary statistics from different genome-wide association studies and investigated overlap in single-nucleotide polymorphisms (SNPs) associated with diabetes-related traits (type 2 diabetes, fasting glucose, fasting insulin, and glycated hemoglobin) and sleep traits (insomnia symptoms, sleep duration, and chronotype) using a conditional/conjunctional false discovery rate approach. Pleiotropic genes were further evaluated for differential expression analysis, and we assessed their expression pattern effects on type 2 diabetes by Mendelian randomization (MR) analysis. Results: We observed extensive polygenic pleiotropy between diabetic traits and sleep traits. Fifty-eight independent genetic loci jointly influenced the risk of type 2 diabetes and the sleep traits of insomnia, sleep duration, and chronotype. The strongest shared locus between type 2 diabetes and sleep straits was FTO (lead SNP rs8047587). Type 2 diabetes (z score, 16.19; P = 6.29 × 10−59) and two sleep traits, sleep duration (z score, −6.66; P = 2.66 × 10−11) and chronotype (z score, 7.42; P = 1.19 × 10−13), were shared. Two of the pleiotropic genes, ENSA and PMPCA, were validated to be differentially expressed in type 2 diabetes, and PMPCA showed a slight protective effect on type 2 diabetes in MR analysis. Conclusions: Our study provided evidence for the polygenic overlap between diabetic traits and sleep traits, of which the expression of PMPCA may play a crucial role and provide support of the hazardous effect of being an “evening” person on diabetes risk.

Variations in lipid levels are the result of combinations of genetic and environmental factors. We aim to investigate the indirect effect between siblings of the three polymorphisms of ADIPOQ on serum lipid levels in rural Chinese populations. A total of 2571 sibling pairs were enrolled as study participants. A generalized estimating equation was used to accommodate a family-based design. We used stratified analysis to detect sex combination differences in the indirect genetic effect. We found a significant association between the number of altered risk alleles of rs182052 and ego lipid levels of TG (β = 0.177, P = 0.003), TC (β = 0.140, P = 0.004) and LDL-C (β = 0.098, P = 0.014). Ego and altered genotypes of rs182052 demonstrated a joint effect on ego lipid levels of TC (β = 0.212, P = 0.019), HDL-C (β = 0.099, P = 0.002) and LDL-C (β = 0.177, P = 0.013) in recessive inheritance mode. In opposite-sex siblings, the altered GG genotype of rs182052 increased the ego lipid levels. Thus, our findings demonstrate that ADIPOQ has an indirect genetic effect on lipid levels in sibling pairs, and there are sex-combination differences in the indirect genetic effect in siblings.

Background: The coronavirus disease 19 (COVID-19) pandemic has become a global threat. Few studies have explored the risk factors for the recovery time of patients with COVID-19. This study aimed to explore risk factors associated with long-term hospitalization in patients with COVID-19.Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 hospitalized in a hospital in Wuhan by March 30, 2020, were included. Demographic, clinical, laboratory, and radiological data from COVID-19 patients on hospital admission were extracted and were compared between the two groups, defined as short- and long-term hospitalization, respectively according to the median hospitalization time. Univariable and multivariable logistic regression methods were performed to identify risk factors associated with long-term hospitalization in patients with COVID-19.Results: A total of 125 discharged patients with COVID-19 were reviewed, including 123 general patients and two severe patients. The median hospitalization time was 13.0 days (IQR 10.0–17.0). Among them, 66 patients were discharged

Few large multicity studies have assessed acute effect of tropospheric ozone pollution on pneumonia risk. We aimed to examine the relation between day-to-day changes in ozone concentrations and hospital admissions for pneumonia in China. We conducted a national time-series study in 184 major Chinese cities from 2014 to 2017. City-specific relation between ozone concentrations and pneumonia admissions was evaluated using an over-dispersed generalized additive model. Random-effects meta-analysis was conducted to pool the city-specific estimates. Two-pollutant models were fitted to test the robustness of the relations. We also investigated potential effect modifiers. Overall, we observed increased admissions for pneumonia associated with ozone exposure. The national-average estimates per 10-μg/m3 increase in ozone were 0.14% (95% CI: 0.03%–0.25%) at lag 0 day in the whole year, 0.30% (95% CI: 0.17%–0.43%) at lag 0 day in the warm season, and 0.20% (95% CI: 0.05%–0.34%) at lag 1 day in the cool season. Two-pollutant models indicated that the ozone effects were not confounded by PM2.5, SO2, NO2 or CO. The association between ozone and pneumonia was stronger in the elderly. Ozone levels and gross domestic product per capita reduced the effects of ozone, and smoking enhanced the effects of ozone. In conclusion, we estimated an increase in daily pneumonia admissions associated with ozone exposure in China. As the first national study in China to report acute effect of ozone on pneumonia hospitalizations, our findings are incredibly meaningful in terms of both ozone pollution related policy development and pneumonia prevention. Keywords: Air pollution, Pneumonia, Ozone, Time-series study

Objective. The genetic variant rs2237895, located in the Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1) gene, has been replicated to be associated with type 2 diabetes mellitus (T2DM) susceptibility, but the relationship with lipids is conflicting. Furthermore, the common genetic predisposition to T2DM and lipids was not fully detected. Methods. In total, 5839 individuals (2220 were T2DM patients) across 2885 families were included. The effect of rs2237895 on T2DM and lipids was estimated using linear regression and logistic regression models after adjustment for multiple covariates. Mediation analysis was then used to test whether KCNQ1 participated in T2DM pathogenesis via lipid-mediated pathways. Results. Per allele-C of rs2237895 was associated with 17% (11-23%, P

BACKGROUND:The effects of ambient particulate matter (PM) pollution on pneumonia in adults are inconclusive, and few scientific data on a national scale have been generated in low- or middle-income countries, despite their much higher PM concentrations. We aimed to examine the association between PM levels and hospital admissions for pneumonia in Chinese adults. METHODS AND FINDINGS:A nationwide time series study was conducted in China between 2014 and 2017. Information on daily hospital admissions for pneumonia for 2014-2017 was collected from the database of Urban Employee Basic Medical Insurance (UEBMI), which covers 282.93 million adults. Associations of PM concentrations and hospital admissions for pneumonia were estimated for each city using a quasi-Poisson regression model controlling for time trend, temperature, relative humidity, day of the week, and public holiday and then pooled by random-effects meta-analysis. Meta-regression models were used to investigate potential effect modifiers, including cities' annual-average air pollutants concentrations, temperature, relative humidity, gross domestic product (GDP) per capita, and coverage rates by the UEBMI. More than 4.2 million pneumonia admissions were identified in 184 Chinese cities during the study period. Short-term elevations in PM concentrations were associated with increased pneumonia admissions. At the national level, a 10-μg/m3 increase in 3-day moving average (lag 0-2) concentrations of PM2.5 (PM ≤2.5 μm in aerodynamic diameter) and PM10 (PM ≤10 μm in aerodynamic diameter) was associated with 0.31% (95% confidence interval [CI] 0.15%-0.46%, P < 0.001) and 0.19% (0.11%-0.30%, P < 0.001) increases in hospital admissions for pneumonia, respectively. The effects of PM10 were stronger in cities with higher temperatures (percentage increase, 0.031%; 95% CI 0.003%-0.058%; P = 0.026) and relative humidity (percentage increase, 0.011%; 95% CI 0%-0.022%; P = 0.045), as well as in the elderly (percentage increase, 0.10% [95% CI 0.02%-0.19%] for people aged 18-64 years versus 0.32% [95% CI 0.22%-0.39%] for people aged ≥75 years; P < 0.001). The main limitation of the present study was the unavailability of data on individual exposure to PM pollution. CONCLUSIONS:Our findings suggest that there are significant short-term associations between ambient PM levels and increased hospital admissions for pneumonia in Chinese adults. These findings support the rationale that further limiting PM concentrations in China may be an effective strategy to reduce pneumonia-related hospital admissions.

Abstract The primary objective of this study was to assess the association between short-term changes in ambient fine particulate matter (PM2.5) and first hospital admissions for ischemic stroke. We identified 63,956 first hospital admissions for ischemic stroke from the Beijing Medical Claim Data for Employees from January 1, 2010, through June 30, 2012. A generalized additive Poisson model was applied to explore the association between PM2.5 and admissions for ischemic stroke. We also explore the effect modification of risk by age and gender. The exposure–response relationship between PM2.5 and admissions for ischemic stroke was approximately linear, with a relatively stable response at lower concentrations (

Soybean is a common food for the Chinese people. We aimed to investigate the risk for brachial ankle pulse wave velocity (baPWV) with inflammatory-related SNPs and soybean. baPWV was measured, and 16 inflammatory-related SNPs located on ADIPOQ, CDH13, SIRT3, SIRT6, CXCL12, CXCR4, NOS1, PON1 and CDKN2B were genotyped in 1749 Chinese participants recruited from various communities. ADIPOQ rs12495941 (GT/TT vs. GG: crude OR = 1.27, p = 0.044) and SIRT6 rs107251 (CT/TT vs. CC: crude OR = 0.74, p = 0.009) were associated with abnormal baPWV (baPWV ≥ 1700 cm/s). After adjustment for conventional environmental risk factors, rs12495941 was associated with abnormal baPWV (GT/TT vs. GG: adjusted OR = 1.43, p = 0.011), but the association between rs107251 and abnormal baPWV was not significant (CT/TT vs. CC: adjusted OR = 0.83, p = 0.173). The interaction between rs107251 and soybean intake for different levels of baPWV was statistically significant (p = 0.017). Compared with a high level of soybean intake, a low level of soybean intake can significantly decrease the risk of abnormal baPWV in individuals of rs107251 CT/TT genotypes (≤100 vs. >100 g/week: adjusted OR = 0.542, p = 0.003). In this study, associations between ADIPOQ rs12495941, SIRT6 rs107251 and baPWV, as well as an interaction between SIRT6 rs107251 and soybean intake for different levels of baPWV were found.