MY-1-Loaded Nano-Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early-Stage ECM via a Hsp47-Dependent Mechanism.

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY-1 is designed and synthesized. To achieve its sustained releasing, the nano-hydroxyapatite (nHA) is chosen as the carrier of MY-1 by mixed adsorption. The results reveal that the sustainable releasing of MY-1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY-1 increases the expression and nuclear translocation of ß-catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY-1 in bone regeneration.

Construction and validation of sheep VASA gene knock-in vector based on CRISPR/Cas9 system / 生物工程学报

This study aimed to explore the expression changes of VASA gene in sheep testis development and to construct VASA gene knock-in vector to prepare for the study on the differentiation of sheep germ cells in vitro. The testicular tissues of 3-month-old (3M) and 9-month-old (9M) sheep which represent immature and mature stages, respectively, were collected. The differential expression of VASA gene was analyzed by quantitative real-time PCR (qPCR) and Western blotting, and the location of VASA gene was detected by immunohistochemistry. The sgRNA targeting the VASA gene was designed and homologous recombination vectors were constructed by PCR. Subsequently, plasmids were transferred into sheep ear fibroblasts. The VASA gene was activated in combination with CRISPR/dCas9 technology to further verify the efficiency of the vector. The results showed that the expression level of VASA gene increased significantly with the development of sheep testis (P < 0.01), and was mainly located in spermatocytes and round spermatids. The knock-in vector of VASA gene was constructed by CRISPR/Cas9 system, and the Cas9-gRNA vector and pEGFP-PGK puro-VASA vector were transfected into ear fibroblasts. After CRISPR/dCas9 system was activated, ear fibroblasts successfully expressed VASA gene. The results suggest that VASA gene plays a potential function in sheep testicular development and spermatogenesis, and the VASA gene knock-in vector can be constructed in vitro through the CRISPR/Cas9 system. Our results provided effective research tools for further research of germ cell development and differentiation.

Chronic myeloid leukemia: the latest progress and future directions / 白血病·淋巴瘤

Chronic myeloid leukemia (CML) is a malignant hematological disease driven by BCR-ABL fusion protein. The emergence of tyrosine kinase inhibitor (TKI) targeting BCR-ABL has completely changed the treatment pattern of CML. From the approval of the first generation TKI imatinib in 2001 to the emergence of the fourth generation TKI drugs, CML patients have benefited a lot from it. But even so, many CML patients suffer treatment failure due to drug resistance, relapse after drug withdrawal or disease progression, some patients therefore are difficult to obtain long-term remission and still need multi-line TKI treatment. The research and development of new drugs covering more mutation lineages, more optimized treatment strategies and drug withdrawal-related research are still the focus of CML treatment. This article introduces the research progress of CML reported on the 64th American Society of Hematology annual meeting.

Periodontitis as a promoting factor of T2D: current evidence and mechanisms / 国际口腔科学杂志·英文版

Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.

Effect of exogenous trivalent iron ions on tau phosphorylation and aggregation in SH-SY5Y cells / 环境与职业医学

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl3) at four concentrations (10, 100, 200, and 400 mg·L−1). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl3 at 10 or 200 mg·L−1. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl3 at 10 and 200 mg·L−1. After dilution with phosphate buffered saline (PBS), FeCl3, human tauR3, and FeCl3 + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl3 and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl3 exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L−1 groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L−1 FeCl3 group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl3 exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L−1 group was up-regulated by 72.7% (P<0.01). After FeCl3-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L−1 group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl3 groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl3 + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.

Analysis of Chemical Constituents in Puerariae Lobatae Radix Dispensing Granules by UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

ObjectiveA rapid method for identification of chemical constituents in Puerariae Lobatae Radix dispensing granules was established in order to clarify the material basis. MethodThe chemical constituents of Puerariae Lobatae Radix dispensing granules was qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） under positive and negative ion modes， and the chromatographic conditions were on an ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as mobile phase for gradient elution（0-4 min， 5%-10%B； 4-10 min， 10%-15%B； 10-20 min， 15%-16%B； 20-27 min， 16%-31%B； 27-33 min， 31%-59%B； 33-42 min， 59%-95%B； 42-42.1 min， 95%-5%B； 42.1-45 min， 5%B）， the flow rate was 0.35 mL·min-1， the column temperature was 40 ℃， the injection volume was 5 μL， and electrospray ionization（ESI） was selected. Then these chemical constituents were comprehensively identified based on PeakView 1.2， PubChem， ChemicalBook， ChemSpider， comparative control profiles and literature information. ResultA total of 128 chemical constituents were identified from the dispensing granules， including 60 flavonoids， 26 organic acids， 7 glycosides， 6 coumarins， 3 nucleosides and 26 other compounds. By focusing on the cleavage patterns of flavonoids， organic acids， glycosides， coumarins， nucleosides and other compounds， 12 compounds that have not been reported in Puerariae Lobatae Radix species were identified from the dispensing granules. ConclusionThe established method can systematically and rapidly identify the chemical constituents in Puerariae Lobatae Radix dispensing granules， and cleared it composition is mainly flavonoids and organic acids. Laying a foundation for the study of the material basis， mechanism of action and clinical application of the dispensing granules.

Analysis of risk factors for the occurrence and in-hospital prognosis in patients with peripartum cardiomyopathy / 中国医师进修杂志

Objective:To investigate the risk factors for the occurrence and poor in-hospital prognosis in patients with peripartum cardiomyopathy (PPCM).Methods:The clinical data of 35 patients with PPCM and 35 healthy pregnant women in Xuanwu Hospital, Capital Medical University and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2003 to January 2022 were retrospectively analyzed. The personal histories, laboratory examination, imaging examination, cardiac function outcome, etc were collected. According to the left ventricular ejection fraction (LVEF) at discharge, the patients with PPCM were divided into in-hospital recovery group (LVEF≥50%, 18 cases) and prolonged disease group (LVEF<50%, 17 cases). Multivariate Logistic regression analysis was used to analyze independent risk factors of poor in-hospital prognosis in patients with PPCM.Results:Among 35 patients with PPCM, the age was (29.81 ± 5.37) years old, 17 cases (48.57%) complicated with gestational hypertension, 6 cases (17.14%) complicated with gestational diabetes mellitus, 24 cases (68.57%) of New York Heart Association (NYHA) cardiac function classification was Ⅲ to Ⅳ class, and 4 cases died (11.43%). The gestational age in patients with PPCM was significantly shorter than that in healthy pregnant women: (36.26 ± 4.27) weeks vs. (38.54 ± 4.59) weeks, the rates of multiple pregnancy and gestational hypertension were significantly higher than those in healthy pregnant women: 17.14% (6/35) vs. 2.86% (1/35) and 48.57% (17/35) vs. 11.43% (4/35), and there were statistical differences ( P<0.05 or <0.01). Compared with hospital recovery group, the patients in protracted disease group had shorter gestational age, larger left ventricular end-diastolic diameter, higher serum creatinine, C-reactive protein and amino-terminal pro-brain natriuretic peptide (NT-proBNP), worse NYHA cardiac function classification, and there were statistical differences ( P<0.05 or <0.01); but there were no statistical difference in LVEF at the first diagnosis and troponin I between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that elevated creatinine was an independent risk factor for poor in-hospital prognosis in patients with PPCM ( OR = 4.554, 95% CI 1.536 to 13.684, P = 0.018). Conclusions:The gestational hypertension may be a risk factor for PPCM. The gestational hypertension, earlier onset time, enlarged left ventricular end-diastolic diameter, high NT-proBNP, high C-reactive protein, high creatinine and high cardiac function NYHA classification may be risk factors for poor in-hospital prognosis in patients with PPCM; and elevated creatinine is an independent risk factor for poor in-hospital prognosis in patients with PPCM.

Application of continuous renal replacement therapy combined with extracorporeal carbon dioxide removal in children with acute respiratory failure / 中华急诊医学杂志

Objective:To explore the role of continuous renal replacement therapy (CRRT) combined with extracorporeal carbon dioxide removal (ECCO 2R) in the treatment of children with respiratory failure. Methods:The clinical data of 12 children with respiratory failure who were treated with CRRT+ECCO 2R in PICU of Jinan Children's Hospital from July 2020 to August 2022 were collected and analyzed retrospectively. The outcomes and the external pipeline usage of the patients were observed, and the blood gas analysis and ventilator parameters before 1 h and after 1, 6, 12 and 24 h of the treatment were compared by one-way ANOVA with LSD post hoc correction. Results:Six patients successfully withdrew from CRRT+ECCO 2R and mechanical ventilation, three patients were transferred to ECMO treatment. Three cases died after voluntary withdrawal of treatment, and two cases died due to treatment failure. The mortality rate was 41.7%. After continuous treatment of CRRT+ECCO 2R for 15 to 112 h, two cases experienced extracorporeal circuit obstruction. After 1 h of treatment, PaCO 2 decreased from (64.67±24.4) mmHg to (49.42±15.54) mmHg, pH increased from (7.28±0.20) to (7.38±0.11), FiO 2 decreased from (0.85±0.13) to (0.78±0.15), PC decreased from (19.42±4.34) cmH 2O to (17.75±4.00) cmH 2O. After 24 h of treatment, PaCO 2 decreased to (39.2±5.55) mmHg, pH increased to (7.41±0.04), FiO 2 decreased to (0.46±0.11), and PC decreased to (13.8±3.36) cmH 2O, and the differences were statistically significant compared with before treatment ( P < 0.05). Conclusions:The combination of CRRT and ECCO 2R therapy can safely substitute for partial lung ventilation/perfusion function, and play a role in protecting right heart function and improving lung-kidney interaction. It can be considered as an option for extracorporeal respiratory, circulatory, and renal support, and consequently has broad prospects.

Development and empirical research of the perioperative fine management evaluation scale for process control / 中华医院管理杂志

Objective:To design an evaluation scale of perioperative fine management, and test it in hospitals, for verifying its effectiveness and sorting out problems in such management.Methods:November 2020 to August 2021, the scale framework was designed by using the process management theories featuring process-oriented control; then the scale was built based on a risk measurement indicators pool created based on policies, literature, standards and expert interview results on perioperative management; an empirical study was made in the end.Results:The scale consists of 209 risk measurement indicators and Likert 5-level scoring method was adopted to measure the possibility of problems in each respect. A total of 99 experts from 31 hospitals participated in the trial of the scale in 2021, and Cronbach α coefficient was 0.997, indicating good consistency among risk measurement indicators. The median of the average scoring of respective risk measurement indicators was 1.69. The most common problems in the perioperative management process include: lack of analysis and countermeasure research on the perioperative fine management; insufficient medical staff; poor awareness of medical staff in standardized and fine management. Conclusions:This scale can quantitatively evaluate respective aspects of perioperative fine management.

Construction and empirical study of clue enrichment model of excessive medical behavior based on the rank assignment method / 中华医院管理杂志

Objective:To construct and verify a model of excessive medical behavior clues enrichment, for the technical support for the safe and rational use of medical insurance fund.Methods:A model of excessive medical behavior clues enrichment was constructed by the rank assignment method. The inpatient transaction records of medical insurance for employees and residents in 5 tumor hospitals in Beijing from 2016 to 2019 were obtained to verify the validity of the model. The patients were grouped according to age and gender, and each transaction record was converted into a standardized score V(0-100 scores), all transactions were divided into 22 groups according to V value. The Cochran-Armitage trend test was used to analyze the variation trend of enrichment rate with the increase of V value. Chi-square test was used to compare the chargeback rates of different groups. The correlation between the standardized score V and the amount of chargeback was tested by Pearson.Results:There were 872 599 and 86 356 hospitalization transactions for employee and resident medical insurance patients, with included 1 164 and 103 chargeback records respectively. The average score and median of V-value of employee and resident medical insurance transactions were scores of 49 and 50 respectively.When V>0, the enrichment rates of the employee and resident medical insurance were on the rise with the increasing of V( Z=23.86, P<0.001; Z=11.02, P<0.001), the refusal rates among different groups was significant different( χ2=1 307.16, P<0.001)and the correlation between V value and the chargeback amount was statistically significant( r=0.29, P<0.001; r=0.30, P=0.003). Conclusions:This study established a clue enrichment model of excessive medical behavior based on the rank assignment method. By analyzing a large number of medical insurance transaction records, the model can focus on the medical insurance transaction with suspected excessive medical treatment behavior, and has a certain guiding role in the management of medical insurance fund.

Influential factors of acute kidney injury after acute myocardial infarction and its effect on adverse cardiovascular events during hospitalization / 中国医师进修杂志

Objective:To observe the incidence and risk factors of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI), and explore the effect of AKI on the adverse cardiovascular events during hospitalization.Methods:The clinical data of 1 286 first-episode patients with AMI from December 2014 to December 2017 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, laboratory test results and used drug were collected, the incidences of AKI and adverse cardiovascular events during hospitalization were recorded.Results:Among 1 286 patients with AMI, 113 cases had AKI, the incidence of AKI was 8.79%. There were statistical differences in gender composition, age, Killip classification>1 grade, hypertension, diabetes, smoking history, left ventricular ejection fraction (LVEF)<56%, baseline estimated glomerular filtration rate (eGFR)<71.5 ml/(min·1.73 m 2), global registry of acute coronary events score (GRACE score) ≥176 scores, hemoglobin<128 g/L, interleukin-6 (IL-6) ≥35.74 ng/L, brain natriuretic peptide (BNP) ≥981 ng/L, thrombolysis in myocardial infarction score (TIMI score) ≥5 scores, high-sensitivity C-reactive protein (hs-CRP) ≥8.44 mg/L, serum creatinine at admission ≥90 μmol/L, heart rate ≥75 times/min and contrast agent dosage/eGFR ≥1.92 between patients with AKI and patients without AKI ( P<0.01 or<0.05). Multivariate Logistic regression analysis result showed that diabetes, LVEF<56%, baseline eGFR< 71.5 ml/(min·1.73 m 2) and hs-CRP ≥8.44 mg/L were the independent risk factors of AKI in patients with AMI ( OR = 2.99, 0.38, 0.30 and 2.48; 95% CI 1.31 to 6.84, 0.16 to 0.88, 0.12 to 0.78 and 1.07 to 5.75; P = 0.010, 0.024, 0.013 and 0.035). The hospital mortality, incidence of adverse cardiovascular events during hospitalization and length of hospital stay in patients with AKI were significantly higher than those in patients without AKI: 11.50% (13/113) vs. 2.39% (28/1 173), 22.12% (25/113) vs. 8.40% (99/1 173) and (12±8) d vs. (10±6) d, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that AKI was the independent risk factors of death and adverse cardiovascular events during hospitalization in patients with AMI ( OR = 5.32 and 3.08, 95% CI 2.67 to 10.59 and 1.89 to 5.03, P<0.01). Conclusions:The incidence of AKI is high in patients with AMI, and previous diabetes history, LVEF<56%, eGFR<71.5 ml/(min·1.73 m 2), hs-CRP≥8.44 mg/L are the independent risk factors of AKI in patients with AMI. The occurrence of AKI after AMI can increase incidence of adverse cardiovascular events during hospitalization and hospital mortality, and prolong the hospital stay.

Chain mediating effect of self-regulated fatigue and psychological distress on the relationship between hypoglycemic fear and self-management in patients with type 2 diabetes / 中国实用护理杂志

Objective:To investigate the status of hypoglycemia fear, diabetes distress, self-regulatory fatigue and self-management in type 2 diabetes patients. The chain mediating effects of self-regulated fatigue and psychological distress on hypoglycemic fear and self-management were investigated.Methods:The Hypoglycemia Fear Survey-Worry Subscale (CHFSII-WS), Diabetes Distress Scale (DDS), Self-Regulatory Fatigue Scale (SRF-S) and Summary of Diabetes Self-Care Activities (SDSCA) were used to investigate the type 2 diabetes patients from the department of Endocrinology of the First Affiliated Hospital in Jinzhou Medical University. And constructed the structural equation model.Results:The scores of fear of hypoglycemia in type 2 diabetes patients were positively correlated with psychological pain and self-regulating fatigue ( r=0.739, 0.625, P<0.05), but negatively correlated with self-management level ( r=-0.602, P<0.05). The psychological pain score was positively correlated with the self-regulating fatigue score ( r=0.669, P<0.05) and negatively correlated with the self-management level score ( r=-0.609, P<0.05). The score of self-regulation fatigue was negatively correlated with the score of self-management ( r=-0.596, P<0.05). Pathway analysis showed that hypoglycemia fear could directly affect self-management behavior, indirectly predict self-management level through self-regulation fatigue and psychological pain respectively, and negatively affect self-management behavior through chain mediation of self-regulation fatigue and psychological pain ( χ2/ df=3.079, GFI=0.920, CFI=0.961, NFI=0.943, IFI=0.961, RMSEA=0.078). Conclusions:The Self-regulated fatigue and psychological distress acts as the chain mediators of hypoglycemic fear and self-management in patients with type 2 diabetes.

Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells.

Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.

A seq2seq model to forecast the COVID-19 cases, deaths and reproductive R numbers in US counties

The global pandemic of coronavirus disease 2019 (COVID-19) has killed almost two million people worldwide and over 400 thousand in the United States (US). As the pandemic evolves, informed policy-making and strategic resource allocation relies on accurate forecasts. To predict the spread of the virus within US counties, we curated an array of county-level demographic and COVID-19-relevant health risk factors. In combination with the county-level case and death numbers curated by John Hopkins university, we developed a forecasting model using deep learning (DL). We implemented an autoencoder-based Seq2Seq model with gated recurrent units (GRUs) in the deep recurrent layers. We trained the model to predict future incident cases, deaths and the reproductive number, R. For most counties, it makes accurate predictions of new incident cases, deaths and R values, up to 30 days in the future. Our framework can also be used to predict other targets that are useful indices for policymaking, for example hospitalization or the occupancy of intensive care units. Our DL framework is publicly available on GitHub and can be adapted for other indices of the COVID-19 spread. We hope that our forecasts and model can help local governments in the continued fight against COVID-19.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naive baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks. Significance StatementThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the US. Results show high variation in accuracy between and within stand-alone models, and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public health action.

Diagnosis of a giant left atrial appendage aneurysm by contrast-enhanced echocardiography: Case report and literature review.

Left atrial appendage aneurysm (LAAA) is a rare pathologic entity that can be congenital or, more frequently, acquired. Its complications include arrhythmias and thromboembolic events, palpitations, hiccups, chest pain, dyspnea, and myocardial infarction. LAAA can be isolated or associated with other congenital anomalies such as atrial septal defect, ventricular septal defect, anomalous renal artery, Noonan syndrome, and Hurler-Scheie syndrome. We report a rare case of giant LAA with intra-aneurysmal thrombus diagnosed by contrast-enhanced echocardiography.

Analysis of the health status, health-related behaviors and health needs of the elderly in China / 中华医院管理杂志

Objective:To investigate the health status, health-related behaviors and health needs of elderlies in eastern, central and western China and to understand their health experience, for exploring an efficient medical service model, and optimizing allocation of medical resources.Methods:This study used the 2008-2018 database from Chinese longitudinal healthy longevity survey organized by Peking University. It described the concentration trend of medical distance by median, compared the health status, health-related behaviors and health needs of the elderly in eastern, central and western China by χ2 tests, and analyzed time-distribution trends of the poor health status, negative health behaviors and health needs by linear relation test. Results:Among 49 611 subjects included in the study, 7 881 of them self-evaluated their health status as poor, 19 445 evaluated their recent health status as deteriorated, while 14 954 lack routine physical examination, 35 141 lack physical exercise, 8 178 smoked, 7 859 drunk, 35 814 had no access to health education services in their communities, 35 676 expressed their health education needs, and 2 637 lack adequate medical services. The difference of distribution of health status, health-related behaviors and health needs of the elderly in eastern, central and western China was statistically significant ( P<0.05). The health status, negative health behaviors and health needs of the elderly in 2008-2018 presented a linear time distribution trend( P<0.05), while the overall medical distance in eastern, central and western China was 1.02 km, 1.00 km and 1.56 km respectively, and the medical distance in the rural area further than that in the urban areas. Conclusions:The health status of the elderly in China needed to be further improved, the proportion of negative health behaviors was high, and the health needs of the elderly in central and western China were large. Promoting an active medical service mode in central and western China, strengthening the interactions between medical institutions and residential communities will contribute to health needs fulfillment and medical resource utilization.

《2020 ESC/HFA Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies》: What is new? / 中华检验医学杂志

Detection of serum biomarkers is an important strategy for the diagnosis of cardiovascular diseases. The roles of serum biomarker detection have become increasingly valuable in the baseline risk stratification among cancer patients in recent years. The Cardio-oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology newly proposed the “role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies”. By evaluating the characteristics of cardiac biomarkers in cancer patients receiving cardiotoxic cancer therapy, this statement discussed the mechanism, clinical application, value on monitoring and prognosis of the two main biomarkers,cardiac troponin and natriuretic peptide on chemotherapy induced cardiac toxic responses. The purpose of this statement is to help establish the multidisciplinary collaborative diagnosis and treatment strategies and provide a clinical framework, and guide clinicians to select appropriate serum biomarker monitoring programs based on risk stratification to prevent cardiovascular disease in cancer patients.

Analysis with the big data of the epidemic trend of acute myocardial infarction in Yichang in 2015-2019 / 公共卫生与预防医学

Objective To investigate the epidemiological characteristics of acute myocardial infarction (AMI) in Yichang City in the last 5 years, and to provide a basis for targeted prevention and treatment. Methods The annual estimated percentage was used to evaluate the trend of morbidity and mortality of AMI by using the monitoring data from 2015 to 2019 from the health big data platform of Yichang. Results There were 1 976 new cases of AMI in Yichang from 2015 to 2019, with a crude morbidity of 41.96/100 000, and standardized morbidity of 87.52/100 000. Among them the crude incidence rate in males was 57.69/100 000, and 29.84/100 000 in females. The difference was statistically significant (χ2=15.76, P2=45.65, P<0.001). The morbidity and mortality of males and females were increased with age. Conclusion From 2015 to 2019, the morbidity of AMI in Yichang was at a moderately low level in China, but the mortality was higher than the national average. The morbidity showed an upward trend, with men and elderly people aged ≥60 being more serious. Appropriate intervention measures should be taken for different groups of people to reduce the incidence of AMI.

Risk factors of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemia / 中华内科杂志

Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.